MÉTODOS PARA TRTAR PÉNFIGO MEDIANTE LA ADMINISTRACIÓN DE (R)-2-[3-[4-AMINO-3-(2 FLUORO-4-FENOXI-FENIL)PIRAZOLO[3,4-D]PIRIMIDIN-1-IL]PIPERIDINA-1-CARBONYL]-4-METIL-4-[4-(OXETAN-3-IL)PIPERAZIN-1-IL]PENT-2-ENONITRILO.

Abstract

This document describes methods for treating pemphigus in a human patient in need comprising administering to the human patient a dose of at least 400 mg of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile (PRN1008) once a day (QD) or twice a day (BID).

Description

Methods to treat pénfigigo through the administration of (r) -2-f3- [4-amino-3- (2fluoro-4-phenoxy-pyenyl) pyrazolo [3.4-d1pirimidin-1-il1piperidine-1-carbonil1-4-methyl-4r4- (oxetan-3-il) pIperazin-1-lease This application claims priority over the US provisional application. UU. No. 62 / 913,029, submitted on October 9, 2019, and provisional application of the United States. This memory describes methods to treat Pénfigo, as, p. eg, vulgar pénfigo (PV) or foliaceous pénfigo (PF), in a human patient who needs it, through administration to the human patient of (R) -2- [3- [4-Am¡no-3- (2-Flore-4-fenox¡-fenil) p¡razolo [3,4-d] p¡r¡mid¡n-1-¡piperidin-1-carbon¡l] -4metil-4- [4- (oxetan-3-il) p¡peraz¡n-1 eg, methods that include administering to the patient a dose of (r) -2- [3- [4-amino-3- (2-fluoro-4-phenoxy-phenyl) p¡razolo [3,4-d] pirim¡d¡n-1il] piperidine-1 -Carbonil] -4-methyl-4- [4- (oxetan-3-il) Pipe. -Il] Pent-2-Enonitrile once a day (QD) or twice a day (IDB). This memory also describes methods to achieve certain results in a population of human patients who are undergoing pénfigo treatment that they understand to administer to each member of the population of human patients (R) -2- [3- [4-amino-3 (2-fluoro-4-fenoxi-fen¡l) p¡razolo [3,4-d] pirimid¡n-1-il] Piper¡d¡na-1-carbon¡l] -4-methyl-4- [4- (oxetan-3-¡¡¡pc) Bruton's Agammaglobulinemia kinase tyrosine (BTK) is an essential signaling element downstream of the BCr (BCR) receptor, FC-gamma receptor (FCyR), and FCépsilon (FCSR) receiver. The BTK is a non -receiver kinase and a member of the family of TEC. BTK is essential for the maturation of the B cell lineage, and the inhibition of BTK activity in cells produces phenotypic changes consisting of BCR block. Illustratively, BTK inhibition results in the downward regulation of various activities of B cells, including proliferation, differentiation, maturation, and cell survival, and the upward regulation of apoptosis. Instead of acting in a “ignition / off switch”, the BTK can be better as a “modulator” of the immune function (Crofford LJ et al., 2016; Pal Singh S et al., 2018). Important information about the BTK function come from the loss of function analysis in humans and mice. Individuals with mutations of loss of function in the BTK gene develop agammaglobulinemia linked to x (xla), characterized by a complete absence of circulating cells and plasma cells, and very low levels of immunoglobulins of all classes (Tsukada 1993, Vetrie 1993). This indicates the potential of BTK inhibition to suppress the production of autoantibodies that is thought to be important in the development of autoimmune diseases, such as, p. eg, vulgar pénfigo (PV). Although BTK is not expressed in T cells, natural murderous cells, and plasma cells and has no traceable direct functions in T cells and plasma cells (Siderras and Smith 1995; Mohamed et al., 2009), the enzyme also regulates the activation of other hematopoietic cells, such rozfrnn / zznz / e / yiai as basophilic, mast cells, macrophages, neutrophils, and platelets. For example, the BTK plays a role in the activation of neutrophils, which are key participants in the inflammatory response that contributes to wound healing, but can also cause tissue damage (Volmering S et al., 2016). According to this, a selective BTK inhibitor has the potential to go to multiple routes involved in inflammation and autoimmunity, including the modulation of the routes of the BCR cells by BCR and the inhibition of the release of cytokines induced by monocytes and macrophages, macrophages, mascitos unworthy induced by FCE, migration of granulocytes. and liberation of mediators. Based on these effects, a selective BTK inhibitor can block the beginning and progression of various inflammatory diseases and mitigate the tissue damage that occurs as a result of these diseases. Although individuals with mutations of loss of function in the BTK gene have a diminished humoral immunity and are susceptible to bacterial and pyrogenous enterovirus infections, which require treatment with intravenous immunoglobulin, it is not predicted that BTK inhibition in individuals with an intact immune system produces a susceptibility similar to infection. Pénfigo is a rare autoimmune disease mediated by B cells that causes weakening intraepithelial blisters and skin erosions and / or mucous membranes. The characteristic intraepidermal ampoules observed in patients with pénfigo are produced by the union of IgG autoantibodies to certain desmosomal adhesion proteins of keratinocytes 1 and 3 (DSG1 and DSG3), giving rise to a loss of cellular adhesion (Amagai M et al., 2012; Díaz la et al., 2000). For example, PV is directed by autoantibodies against epidermal proteins. The pénfigo affects approximately to.-0.1-0.5 / 100,000 people each year and has a 10 %mortality rate, generally due to infections that arise from compromised tissues and side effects of the treatment (Scully et al., 2002; Scully et al., 1999). As the Pénfigo is a chronic disease for which there is no cure, most patients with pénfigo are existing cases. The current starting standard for recent starting pénfigo is a high dose of corticosteroids (CS) (0.5-1.5 mg / kg / day) (Murrell DF et al., 2018), alone or in combination with other immunosuppressive drugs such as rituximab, mofetyl mycophenolate, or azathioprine (kasperkiewicz m et al. 2017). Illustratively, the PV responds acutely to the anti-inflammatory effects of corticosteroids and in 5 to 35 weeks to the depletion of B cells by anti-CD20 therapy (Horvath et al. 2012). The rituximab, a chimeric monoclonal antibody in front of the marker of the surface of the B cells, CD20, has been recently approved by the FDA and the European Medication Agency (EMA) for the treatment of vulgar pénfigo (PV) of moderate to serious on the basis of studies carried out in freshly diagnosed patients with improved full remission rates (CR) without steroid / treatment in comparison (JOLY P et al., 2017; Information on prescription of Rituxan; Cianchini et al., 2007). However, patients treated with rituximab still require doses of moderate to high steroid (PF). Other treatments for pénfigo such as Intravenous Immunoglobulin (MG), Plasmapheresis, and extracorporeal photopheresis (Harman Ke et al., 2017) have some benefits, but they should still be evaluated in randomized controlled tests or major populations of patients (Amagai M et al., 2009; Martin Lk et al., 2009). Therefore, immunomodulatory therapies of rapid action are very necessary, with reduction of steroid dose, and conveniently administered with improved safety profiles. B cells play key roles in the production of autoantibodies involved in the pathology of the Pénfigo and in the mechanisms of cell tolerance, thus presenting themselves as an attractive target for the treatment of the pénfigo. For example, BTK inhibition is a striking therapeutic strategy for the pénfigo. Several BTK (BTKI) inhibitors administered orally, including Ibrutinib (PCI-32765) and Spebrutinib (CC-292), are currently marketed or in clinical development for a range of indications (Lee A et al., 2017). For example, Ibrutinib has provided additional clinical validation of Diana BTK and has been recently approved for use in humans in mantle cell lymphoma, Waldestróm macroglobulinemia, and chronic lymphocytic leukemia by the Food and Food Administration of the US (Wang 2013, Byrd 2013, Prospect of Imbuvica, 2015). In addition, it has been reported that CC292 is well tolerated in a population of healthy dose volunteers that provide a 100 % occupation of the BTK enzyme (Evans 2013). In addition, Evobrutinib has recently demonstrated effective sclerosis in a phase 2 (Montalban X et al., 2019). Other BTKI compounds are in clinical development for various disorders mediated by immunity, such as immune thrombocytopenia (NCT03395210), rheumatoid arthritis (NCT03823378, NCT03682705, NCT03233230), and asthma (NCT039444707) (MONTALBAN X et al. 2019; Although the covalent BTKI, such as Ibrutinib and Acalabrutinib, improved with respect to selectivity issues that characterize many first -generation kinase inhibitors, these inhibitors are typically irreversible, causing a permanent modification of both target and non -target and side effects such as thrombocytopenia, anemia, platelet aggregation, and hepatotoxicity, and hepatotoxicity (Inframation on prescription of Rituxan, 2018; Drug Record Kinase Inhibitors, 2019; Khan and et al., 2019; Paydas S, 2019; Imbuvica, 2013; Rigg ra et al., 2016; Tang CPS et al., 2018). Therefore, there is a need for treatment modalities for immunity mediated diseases, such as, p. eg, Pénfigo, based on BTKI with reduced side effects. The compound (i) is a BTK inhibitor with the following structure: Rozfrnn / ZZNZ / E / Yiai Rozfrnn / ZZNZ / E / Yiai where *C is a stereochemical center. See PCT Publication No. WO 2014 / 039899, ​​which is incorporated into this memory by reference, p. eg, example 31. He (R) -2- [3- [4-Am¡no-3- (2-Fluoro-4-fenox Erid¡na-1-carbon¡l] -4met¡l-4- [4- (oxetan-3-¡l) p¡perazin-1-¡l] pent-2-enon that has the following structure: It is also known as PRN1008 and Rilzabrutinib. This compound has been described in several patent publications, such as, p. eg, PCT Publications No. WO2014 / 039899, ​​WO2015 / 127310, WO2016 / 100914, WO 2016 / 105531, and WO2018 / 005849, the contents of each of which are incorporated by reference in this memory. PRN1008 is a new inhibitor, which is a small, highly selective molecule of the signaling of white blood cells other than T cells through the signaling of the receptor of the B, FCyR cells, and / or FCE of the BTK route. PRN1008 functions as a reversible covalent BTK inhibitor and forms a union both non -covalent and covalent with its target, allowing augmented selectivity and prolonged inhibition. Compared to the first and second generation BTKI, PRN1008 has shown a minimum cross reactivity with other molecules and has a low risk of effects outside the target (Smith PF Etal., 2017). In an important way, the reversible union of PRN1008 minimizes the probability of permanently modified peptides (Serafimova IM 2012). PRN1008 has shown promising results for the treatment of immunity mediated diseases. PRN1008 is the most advanced BTKI in terms of development for an autoimmune disease (phase 3, NCT03762265) and the first BTKI to be evaluated in the treatment of the Pénfigo. In PRN1008 phase 1 studies with 114 healthy volunteers, Diana BTK's occupation levels were overcome safely and consistently, suggesting that PRN1008 can be highly effective in human pénfigo and other autoimmune diseases. In addition, preclinical and clinical PD / PD data showed that the effects of treatment remained even after the compound was clarified from the circulation, consisting of a residence time in the prolonged target (Hill R et al., 2015) and high occupancy rate (> 90 % in four hours) (Smith Pf et al., 2015.) PRN1008 has also demonstrated a favorable second profile. On the basis of preclinical studies of reproductive toxicity, PRN1008 is not expected to damage fetal development or male fertility. In a phase 1 study in healthy volunteers, the most commonly reported adverse events were gastrointestinal adverse events, including nausea / vomiting and diarrhea. No serious adverse events or deaths were reported, and no patient discontinued the treatment due to an adverse event (Smith PF 2017). On January 18, 2018, PRN1008 had been administered to 21 patients with pénfigo (vulgar pénfigo (PV) and foliaceous pénfigo (PF)), 18 of which had 4 or more weeks of treatment with PRN1008. PRN1008 was well tolerated in this study. Of the 18 patients with efficiency data, 11 (61 %) fulfilled the primary final point of “control of the disease activity” (CDA) with a dose of corticosteroid (CS) of <0.5 mg / kg / day (low dose of CS) on the visit of week 5. Three patients got CDA without CS. Two patients required high doses of CS temporarily during treatment with PRN1008 due to the worsening of the disease activity. Four patients got the full remission (CR) with 1 to 20 mg / day of CS, three got CR in week 13 (25 %), and one got CR in week 21. The efficiency effects of PRN1008 are produced through three simultaneous mechanisms of action: anti -inflammatory effects; Neutralization of pathogenic autoantibodies; and blocking the production of autoantibodies. PRN1008 inhibits inflammatory cellular activities in mast cells and neutrophils (Langrish C et al., 2019). It also neutralizes autoimmune responses by blocking the signals of the FE region of the antibodies and reduces the generation of autoantibodies by blocking the activation and maturation of B cells (LANGRISH C et al., 2019; LANGRISH CL et al., 2017). These effects occur without directly impact on T cells or cause the depletion of B cells. (Langrish Cl et al., 2017). In this memory the results of phase 2 studies with PRN1008 are discussed for the treatment of PV and PF. This memory describes methods to treat pénfigo in a human patient who needs it to understand the human patient a dose of at least 400 mg of (R) -2- [3- [4 amino-3- (2-fluoro-4-phenoxi-fenil) p¡razolo [3,4-d] p¡rimidin-1-il] piper¡dina-1-carbon¡l] -4-methyl-4- [4- (oxetan-3il) piperaz (QD) for at least 14 days. In some modalities, a dose of at least 400 mg of PRN1008 QD for 14 to 168 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 QD for 14 days is administered to the human patient. In some modalities, the patient Rozfrnn / ZZNZ / E / YIAI HUMAN is administered a dose of at least 400 mg of PRN1008 QD for 28 days. In some modalities, a dose of at least 400 mg of PRN1008 QD for 84 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 QD for 168 days is administered to the human patient. In some modalities, the methods include administering the human patient a 400 mg dose of PRN1008 QD for at least 14 days. In some modalities, a dose of 400 mg of PRN1008 QD is given to the human patient for 14 to 168 days. In some modalities, a dose of 400 mg of PRN1008 QD for 14 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 QD for 28 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 QD for 84 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 QD for 168 days is administered to the human patient. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 once a day (QD) for 14 days; and administer to the human patient a second dose of 400 mg of PRN1008 twice a day (IDB) for at least 14 days after the administration of the first dose. In some modalities, a second dose of 400 mg of PRN1008 IDB for 14 to 154 days after administration of the first dose is administered to the human patient. In some modalities, PRN1008 is administered to the human patient for a maximum of 168 days. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 once a day (QD) for 14 days; and administer to the human patient a second dose of 400 mg of PRN1008 twice a day (IDB) for 14 days after the administration of the first dose; and administer to the human patient a third dose of 600 mg of PRN1008 twice a day (IDB) after the administration of the second dose. In some modalities, a third dose of 600 mg of PRN1008 IDB for a maximum of 140 days after the administration of the second dose is administered to the human patient. In some modalities, a third dose of 600 mg of PRN1008 IDB for 56 days after the administration of the second dose is administered to the human patient. In some modalities, PRN1008 is administered to the human patient for a maximum of 168 days. In some modalities, the methods include administering PRN1008 in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day). In some modalities, the first corticosteroid is chosen from prednisone, prednisolone, and methylprednisolone. Rozfrnn / ZZNZ / E / Yiai In some modalities, the human patient is characterized by unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by vulgar unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by unrelated or recurrent foliaceous pénfigo before the PRN1008 administration. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo (PDAI) disease activity from 8 points to 60 points before the PRN1008 administration. In some modalities, the human patient is characterized by a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid before the administration of PRN1008. In some modalities, the second corticosteroid is chosen from prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid is the same as the second corticosteroid. In some modalities, the first corticosteroid is not the same as the second corticosteroid. In some modalities, PRN1008 includes the isomer (e) of (R) -2- [3- [4-amino-3- (2-fluoro-4fenox¡-fen¡l) pyrazolo [3,4-d] p¡r¡mid¡n-1-il] p¡per¡d¡na-1-carbon¡l] -4-meth¡l-4- [4- (oxetan-3-il) p¡peraz¡n-1- In some modalities, PRN1008 includes the isomer (z) of (r) -2- [3- [4-amino-3- (2-fluoro4-fenox¡-phenyl) pyrazolo [3,4-d] p¡r¡midin-1 -Il] piperidin-1 -Carbonil] -4-metil-4- [4- (oxetan-3-3-¡ -Il] Pent2 -Enonitrilo. In some modalities, PRN1008 includes a mixture of isomers (e) and (z) of (R) 2- [3- [4-amino-3- (2-fluoro-4-fenoxi-fen¡l) p¡razolo [3,4-d] p¡rimid¡n-1-¡l] p¡per¡dina-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-il) p¡peraz¡n-1-il] pent-2-in. In some modalities, the methods include treating vulgar pénfigo. In some modalities, the methods include treating foliaceous pénfigo. This memory also describes methods to treat pénfigigo in a human patient that needs it to understand the human patient a dose of at least 400 mg of (R) -2 [3- [4-am ¡no-3- (2-fluoro-4-phenox¡-pen¡l) pyrazol day (IDB) for at least 14 days. In some modalities, a dose of at least 400 mg of PRN1008 IDB for 14 to 84 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 IDB for 14 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 IDB for 28 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 IDB for 84 days is administered to the human patient. In some modalities, the methods include managing the human patient a dose of 400 mg of PRN1008 IDB for at least 14 days. In some modalities, a dose of 400 mg of PRN1008 BID for 14 to 84 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 BID for 14 days is administered to the human patient. In some modalities, a dose of Rozfrnn / ZZNZ / E / YIAI is administered to the human patient 400 mg of PRN1008 BID for 28 days. In some modalities, a dose of 400 mg of PRN1008 BID for 84 days is administered to the human patient. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 twice a day (IDB) for at least 14 days; and administer to the human patient a second dose of 500 mg of PRN1008 twice a day (IDB) after the administration of the first dose. In some modalities, a first dose of 400 mg of PRN1008 IDB for 14 to 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for more than 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for 33 days is administered to the human patient. In some modalities, PRN1008 is administered to the human patient for a maximum of 84 days. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 twice a day (IDB) for at least 14 days; and administer to the human patient a second dose of 600 mg of PRN1008 twice a day (IDB) after the administration of the first dose. In some modalities, a first dose of 400 mg of PRN1008 IDB for 14 to 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for more than 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for 22 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for 56 days is administered to the human patient. In some modalities, PRN1008 is administered to the human patient for a maximum of 84 days. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 twice a day (IDB) for at least 14 days; Administer to the human patient a second dose of 500 mg of PRN1008 twice a day (IDB) for at least 14 days after the administration of the first dose; and administer to the human patient a third dose of 600 mg of PRN1008 twice a day (IDB) after the administration of the second dose. In some modalities, a first dose of 400 mg of PRN1008 IDB for 14 to 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for more than 28 days is administered to the human patient. In some modalities, a second dose of 500 mg of PRN1008 IDB for 14 to 28 days after the administration of the first dose is administered to the human patient. Rozfrnn / ZZNZ / E / Yiai In some modalities, PRN1008 is administered to the human patient for a maximum of 84 days. In some modalities, the methods include administering PRN1008 in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day). In some modalities, the first corticosteroid is chosen from prednisone, prednisolone, and methylprednisolone. In some modalities, the human patient is characterized by unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by vulgar unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by unrelated or recurrent foliaceous pénfigo before the PRN1008 administration. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo (PDAI) disease activity from 8 points to 60 points before the PRN1008 administration. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo (PDAI) disease activity from 8 points to 45 points before the PRN1008 administration. In some modalities, the human patient is characterized by a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid before the administration of PRN1008. In some modalities, the second corticosteroid is chosen from prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid is the same as the second corticosteroid. In some modalities, the first corticosteroid is not the same as the second corticosteroid. In some modalities, PRN1008 includes the isomer (e) of (R) -2- [3- [4-amino-3- (2-fluoro-4fenox¡-fen¡l) p¡razolo [3,4-d] p¡r¡mid¡n-1-¡l] Piper¡d¡na-1-carbon¡l] -4-meth¡l-4- [4- (oxetan-3-¡l) Pipe. In some modalities, PRN1008 includes the isomer (Z) of (R) -2- [3- [4-amino-3- (2-fluoro4-fenox¡-phenyl) pyrazolo [3,4-d] pir¡midin-1-il] piperidine-1-carbonil] -4-methyl-4- [4- (oxetan-3-il) pent-il] pent2-initrile. In some modalities, PRN1008 includes a mixture of isomers (e) and (z) of (R) 2- [3- [4-Am¡no-3- (2-Flore-4-fenox¡-fenil) P¡razolo [3,4-d] p¡r In some modalities, the methods include treating vulgar pénfigo. In some modalities, the methods include treating foliaceous pénfigo. Example modalities 1: Without limitation, some description modalities include: 1. A method to treat a pénfigo in a human patient who needs it to understand the human patient a dose of at least 400 mg of (r) -2- [3- [4-amino-3- (2-Fluoro-4-fenox¡ rozfrnn / zznz / e / yiai phenyl) pyrazolo [3,4-d] pirimidin-1 -Ill] piperidin -Carbonil] -4-methyl-4- [4- (Oxetan-3-il) Piperazin-1 -Il] Pent-2enitrile (PRN1008) once a day (QD) for at least 14 days. 2. The method of modality 1, which includes administering to the human patient a dose of at least 400 mg of PRN1008 QD for 14 to 168 days. 3. The method of modality 1 or 2, which includes administering to the human patient a dose of at least 400 mg of PRN1008 QD for 14 days. 4. The method of modality 1 or 2, which includes administering to the human patient a dose of at least 400 mg of PRN1008 QD for 28 days. 5. The method of modality 1 or 2, which includes administering to the human patient a dose of at least 400 mg of PRN1008 QD for 84 days. 6. The method of modality 1 or 2, which includes administering to the human patient a dose of at least 400 mg of PRN1008 QD for 168 days. 7. The method of modality 1, which includes administering to the human patient a dose of 400 mg of PRN1008 QD for at least 14 days. 8. The method of modality 1 or 7, which includes administering to the human patient a dose of 400 mg of PRN1008 QD for 14 to 168 days. Rozfrnn / ZZNZ / E / Yiai 9. The method of any of the modalities 1, 7, or 8, which includes administering to the human patient a dose of 400 mg of PRN1008 QD for 14 days. 10. The method of any of the modalities 1, 7, or 8, which includes administering to the human patient a dose of 400 mg of PRN1008 QD for 28 days. 11. The method of any of the modalities 1, 7, or 8, which includes administering to the human patient a dose of 400 mg of PRN1008 QD for 84 days. 12. The method of any of the modalities 1, 7, or 8, which includes administering to Human patient A dose of 400 mg of PRN1008 QD for 168 days. 13. The method of modality 1, which includes: Administer to the human patient a first dose of 400 mg of PRN1008 QD for 14 days; and administer to the human patient a second dose of 400 mg of PRN1008 twice a day (IDB) for at least 14 days after the administration of the first dose. 14. The method of modality 13, which includes administering to the human patient a second dose of 400 mg of PRN1008 IDB for 14 to 154 days after the administration of the first dose. 15. The method of modality 1, which includes: Administer to the human patient a first dose of 400 mg of PRN1008 QD for 14 days; and administer to the human patient a second dose of 400 mg of PRN1008 twice a day (IDB) for 14 days after the administration of the first dose; and administer to the human patient a third dose of 600 mg of PRN1008 BID after the administration of the second dose. 16. The method of modality 15, which includes administering to the human patient a third dose of 600 mg of PRN1008 IDB for 140 days maximum after the administration of the second dose. 17. The method of modality 15, which includes administering to the human patient a third dose of 600 mg of PRN1008 IDB for 56 days after the administration of the second dose. 18. A method to treat a pénfigo in a human patient who needs it to understand to administer to the human patient a dose of at least 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenox (IDB) for at least 14 days. 19. The method of modality 18, which includes administering to the human patient a dose of at least 400 mg of PRN1008 IDB for 14 to 84 days. 20. The method of modality 18 or 19, which includes administering to the human patient a dose of at least 400 mg of PRN1008 IDB for 14 days. 21. The method of modality 18 or 19, which includes administering to the human patient a dose of at least 400 mg of PRN1008 IDB for 28 days. 22. The method of modality 18 or 19, which includes administering to the human patient a dose of at least 400 mg of PRN1008 IDB for 84 days. 23. The method of modality 18, which includes administering to the human patient a dose of 400 mg of PRN1008 IDB for at least 14 days. 24. The method of modality 18 or 23, which includes administering to the human patient a dose of 400 mg of PRN1008 IDB for 14 to 84 days. 25. The method of any of the modalities 18, 23, or 24, which includes administering to the human patient a dose of 400 mg of PRN1008 BID for 14 days. 26. The method of any of the modalities 18, 23, or 24, which includes administering to the human patient a dose of 400 mg of PRN1008 BID for 28 days. 27. The method of any of the modalities 18, 23, or 24, which includes administering to the human patient a dose of 400 mg of PRN1008 BID for 84 days. 28. The method of modality 18, which includes: Administer to the human patient a first dose of 400 mg of PRN1008 BID for at least 14 days; and administer to the human patient a second dose of 500 mg of PRN1008 BID after the administration of the first dose. 29. The method of modality 28, which includes administering to the human patient a first dose of 400 mg of PRN1008 IDB for 14 to 28 days. 30. The method of modality 28, which includes administering to the human patient a first dose of 400 mg of PRN1008 IDB for more than 28 days. 31. The method of modality 28, which includes administering to the human patient a first dose of 400 mg of PRN1008 IDB for 33 days. 32. The method of any of the modalities 28-31, where PRN1008 is administered to the Rozfrnn / ZZNZ / E / Yiai human patient for a maximum of 84 days. 33. The method of modality 18, which includes: Administer to the human patient a first dose of 400 mg of PRN1008 BID for at least 14 days; and administer to the human patient a second dose of 600 mg of PRN1008 BID after the administration of the first dose. 34. The method of modality 33, which includes administering to the human patient a first dose of 400 mg of PRN1008 IDB for 14 to 28 days. 35. The method of modality 33 or 34, which includes administering to the human patient a first dose of 400 mg of PRN1008 IDB for 22 days. 36. The method of modality 33, which includes administering to the human patient a first dose of 400 mg of PRN1008 IDB for more than 28 days. 37. The method of modality 33 or 36, which includes administering to the human patient a first dose of 400 mg of PRN1008 IDB for 56 days. 38. The method of any of the modalities 33-37, where PRN1008 is administered to the human patient for a maximum of 84 days. 39. The method of modality 18, which includes: Administer to the human patient a first dose of 400 mg of PRN1008 BID for at least 14 days; Administer to the human patient a second dose of 500 mg of PRN1008 BID for at least 14 days after the administration of the first dose; and administer to the human patient a third dose of 600 mg of PRN1008 BID after the administration of the second dose. 40. The method of modality 39, which includes administering to the human patient a first dose of 400 mg of PRN1008 IDB for 14 to 28 days. 41. The method of modality 39 or 40, which includes administering to the human patient a second dose of 500 mg of PRN1008 IDB for 14 to 28 days after the administration of the first dose. 42. The method of any of the modalities 39-41, where PRN1008 is administered to the human patient for a maximum of 84 days. 43. The method of any of the modalities 1-42, which includes administering PRN1008 in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day. 44. The method of modality 43, where the first corticosteroid is chosen from prednisone, prednisolone, and methylprednisolone. 45. The method of any of the modalities 1-44, where the human patient is characterized by unrelated or recurrent pénfigo before the administration of PRN1008. 46. ​​The method of any of the modalities 1-45, where the human patient is characterized by vulgar pénfigo without treating or recurrent before the administration of PRN1008. Rozfrnn / ZZNZ / E / Yiai 47. The method of any of the modalities 1-46, where the human patient is characterized by without treating foliaceous pénfigo before the administration of PRN1008. 48. The method of any of the modalities 1-47, where the human patient is characterized by a skin score of the Pénfigo disease activity (PDAI) index from 8 points to 60 points before the administration of PRN1008. 49. The method of any of the modalities 1-48, where the human patient is characterized by a maintenance dose of less than or equal to 0.5 mg / kg / day of a second corticosteroid before the administration of PRN1008. 50. The method of modality 49, where the second corticosteroid is chosen from prednisone, prednisolone, and methylprednisolone. 51. The method of modality 49 or 50, where the first corticosteroid is the same as the second corticosteroid. 52. The method of modality 49 or 50, where the first corticosteroid is not the same as the second corticosteroid. 53. The method of any of the modalities 1-52, where PRN1008 includes the isomer (e) of (R) -2- [3- [4-am ¡no-3- (2-Fluoro-4-fenoxi-fen¡l) p¡razolo [3,4-d] pirim¡d¡n-1-¡l] p¡perid¡na-1carbonil] -4-methyl-4- [4- (oxetan-3-il) p¡peraz¡n-1-¡ 54. The method of any of the modalities 1-52, where PRN1008 includes the isomer (Z) of (R) -2- [3- [4-am ¡no-3- (2-Fluoro-4-fenox¡-fenil) pyrazolo [3,4-d] pjr¡midin-1-il] Piper¡d¡na-1carbon¡l] -4-meth¡l-4- [4- (oxetan-3-¡l) Piperaz¡n-1-il] pent-2-in. 55. The method of any of the modalities 1-52, where PRN1008 includes a mixture of the isomers (e) and (z) of (R) -2- [3- [4-Am¡no-3- (2-Flore-4-fenox Rid¡na-1-carbon¡l] -4-meth¡l-4- [4- (oxetan-3-¡¡p¡perazin-1-¡l] pent-2-enon¡tr¡lo. 56. The method of any of the modalities 1-55, which includes treating vulgar pénfigo. 57. The method of any of the modalities 1-55, which includes treating foliaceous pénfigo. 58. The method of any of the modalities 1-57, which includes reducing the average daily use of corticosteroids by the human patient. 59. The method of modality 58, which includes reducing the average daily use of corticosteroids by the human patient at least 20 %. 60. The method of modality 58, which includes reducing the average daily use of corticosteroids by the human patient at least 50 %. 61. The method of any of the modalities 1-60, which includes healing established pénfigo injuries. 62. The method of modality 61, which includes cure at least 50 % of established pénfigo lesions. 63. The method of any of the modalities 1-62, which includes preventing the formation of new pénfigo injuries. 64. The method of any of the modalities 1-63, which includes reducing a Rozfrnn / ZZNZ / E / Yiai Cutaneous score of the index of the Pénfigo disease activity (PDAI). 65. The method of modality 64, which includes reducing a pdai skin score at least 20 %. 6 67. The method of modality 66, where the human patient is characterized by a PDAI cutaneous score of 0 after the administration of PRN1008. 68. The method of modality 66, where the human patient is characterized by a PDAI cutaneous score of 1 after the administration of PRN1008. 69. The method of any of the modalities 1-60, which also includes controlling the activity of Pénfigo's disease. 70. The method of any of the modalities 1-60, which also includes getting an end to the Pénfigo consolidation phase. 71. The method of mode 70, where more than 60 % of established pénfigo lesions have been cured. 72. The method of any of the modalities 1-60, which includes achieving a complete remission. 73. The method of any of the modalities 1-72, where PRN1008 is orally administered to the human patient. 74. The method of any of the modalities 1-73, where PRN1008 is administered to the human patient in the form of at least one tablet. 75. The method of modality 74, where PRN1008 is administered with a glass of water. 76. The method of any of the modalities 1-75, where PRN1008 is administered with food. 77. The method of any of the modalities 1-75, where PRN1008 is administered without food. Example modalities 2: Without limitation, some description modalities include: 1. A method to treat a human patient suffering from vulgar pénfigo (PV) or foliaceous pénfigo (PF) that includes: Administer to the patient a dose of 400 mg of (r) -2- [3- [4-amino-3- (2-fluoro-4-phenox¡fenil) pyrazolo [3,4-d] pirimidin-1 -Il] piperidine-1 -Carbonll] -4-meth¡l-4- [4- (oxetan-3-¡l) Pipe. (PRN1008) Once a day (QD) for a minimum of 14 days up to a maximum of 168 days. 2. The method of modality 1, which also includes managing the patient a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day). 3. The method of modality 1 or 2, where PRN1008 is administered to the patient during 14 Rozfrnn / ZZNZ / E / Yiai days. 4. The method of modality 1 or 2, where PRN1008 is administered to the patient for 28 days. 5. The method of modality 1 or 2, where PRN1008 is administered to the patient for 84 days. 6. The method of modality 1 or 2, where PRN1008 is administered to the patient for 168 days. 7. The method of modality 1 or 2, which also includes increasing the dose of PRN1008 after 14 days up to 400 mg twice a day (IDB) for a minimum of 14 days up to a maximum of 154 days. 8. The method of modality 7, which also includes staggering the dose of PRN1008 after 14 days up to 600 mg IDB to a maximum of 140 days. 9. The method of modality 8, where the dose of 600 mg IDB is administered for 56 days. 10. The method of any of the modalities 1-9, where before the administration of 400 mg QD of PRN1008, the patient is maintained with a low dose of corticosteroid (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. 11. The method of any of the modalities 1 -10, where before the administration of 400 mg QD of PRN1008, the patient has (a) without treating or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points. 12. The method of modality 2 or 10, where corticosteroid is prednisone, prednisolone, or methylprednisolone. 13. The method of any of the modalities 1-12, where PRN1008 includes a mixture of the isomers (e) and (z) of (R) -2- [3- [4-Am 14. A method to achieve a final point prevails in 27 % to 29 % of a population of human patients who are undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering to the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2fluoro-4-fenoxi-fen¡l) p¡razolo [3,4-d] pirim¡din-1-¡l] p¡per¡dina-1-carbon¡l] -4-meth¡l-4- [4- (oxetan-3-¡l) p¡peraz Once a day (QD) for 14 days in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where before the administration of 400 mg QD of PRN1008, the patient population has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. 15. A method to achieve a primary end point in 43 % of a population of patients Rozfrnn / ZZNZ / E / Yiai Human (R) -2- [3- [4-amino-3- (2-fluoro-4-phenox (PRN1008) Once a day (QD) for 28 days, where the population of patients throughout the PRN1008 administration is also administered to the population of patients a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. 16. A method to achieve a primary end point in 50 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenoxyphenyl) Pyrazol where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. 17. A method to achieve a primary end point in 53 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenox (PRN1008) Once a day (QD) for 14 days, followed by the staggered increase in the PRN1008 dose to 400 mg IDB for 14 days, where throughout the administration of PRN1008 to the population of patients, the population of patients is also administered to the population of patients a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF and Rozfrnn / ZZNZ / E / Yiai lesions ceases to heal the established PV and PF lesions. 18. A method to achieve a primary end point in 80 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-fenox¡fen¡l) p¡razolo [3,4-d] p¡r¡m¡d¡n-1-¡l] p¡per¡d¡na-1-carbonil] -4-methyl-4- [4- (oxetan-3-¡l) p¡peraz (PRN1008) Once a day (QD) for 14 days, followed by the stepped increase in the DOS or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. 19. A method to achieve the complete remission of the disease in 7 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4 amino-3- (2-fluoro-4-fenoxi-fen¡l) p¡razolo [3,4-d] pirimidin-1-il] p¡per¡dina-1-carbon¡l] -4-methyl-4- [4- (oxetan-3il) piperaz (QD) for 84 days, where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. 20. A method to achieve the complete remission of the disease in 13 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceo pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4 am ¡no-3- (2-Flore-4-fenox¡-phenyl) pyrazolo [3,4-d] pirim¡din-1-il] Piperid¡na-1-carbonil] -4-meth¡l-4- [4- (oxetan-3¡l) Pieperazin-1-il] pent-2-initrile (PRN1008) once a day once a day (QD) for 14 days, followed by the staggered increase in the Dose of PRN1008 to 400 mg IDB for 14 days, followed in addition to the stepped increase in the dose up to 600 mg IDB for 56 days, where the population of patients is also administered to the PRN1008 administration, the population is also administered to the population of patients a corticosteroid at a dose of less than or equal to 0.5 mg / kg / kg / day 0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid to a Rozfrnn / ZZNZ / E / Yiai dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PVOPF injuries. 21. A method to achieve the complete remission of the disease in 40 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4 am¡no-3- (2-fluoro-4-fenox¡-fen¡l) pyrazol Day (QD) for 14 days, followed by the staggered increase in the dose of PRN1008 up to 400 mg IDB for 14 days, in addition to the stepped increase in the dose up to 600 mg IDB for 140 days, and subsequently submit the population of patients to post -treatment follow -up for 28 days, during that follow -up, the population of PRN1008 patients is not administered; where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. 22. A method to treat vulgar pénfigo (PV) or pénfigigo or foliage pénfigo (PF) in a population of patients that the population will administer a dosing regime as follows: administer (r) -2- [3- [4-amino-3- (2-fluoro-4-fenoxi-fenil) pyrazolo [3,4-d] p¡rimidin-1 carbonil] -4-meth¡l-4- [4- (oxetan-3-il) piperaz¡n-1-¡pent-2-enon¡tril Week 25; where the condition for the stepped increase in the dose is fine (a) The patient is not achieving control of the disease activity (CDA) or (b) is not reaching the end of the consolidation phase (ECP); where the control of the disease activity is defined as the visit in which the formation of new PV or PF injuries ceases and the established PV or PF lesions begin to be cured; where the end of the consolidation phase is defined as the visit in which new PV or PF injuries have not been developed for a minimum of 2 weeks and most of the established PV or PF lesions have been cured; where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. Rozfrnn / ZZNZ / E / Yiai 23. A method to treat a human patient suffering from vulgar pénfigo (PV) or foliaceous pénfigo (PF) that includes: Administer to the patient a 400 mg dose of (R) -2- [3- [4-amino-3- (2-fluoro-4-fenox¡fen¡l) p¡razolo [3,4-d] p¡nm¡d¡n-1-¡l] p¡per¡d¡na-1-carbonil] -4-meth¡l-4- [4- (oxetan-3-¡l) p¡peraz¡n-1-¡ (PRN1008) Twice a day (IDB) for 168 days, where throughout the administration of PRN1008, a corticosteroid is also given to the patient at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg IDB of PRN1008, the patient has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. 24. The method according to any of the modalities 14-23, where corticosteroid is prednisone, prednisolone, or methylprednisolone. 25. The method according to any of the modalities 14-24, where PRN1008 comprises a mixture of the isomers (e) and (z) of (r) -2- [3- [4-am ¡no-3- (2-Fluoro-4-fenoxi-fen¡l) pyrazolo [3,4-d] pir¡m¡d -Carbonil] -4-methyl-4- [4- (oxetan-3-il) p¡peraz¡n-1 -Il] Pent-2-enonitrile. 26. The method according to any of the modalities 14-25, where after the administration of PRN1008, the patient has a PDAI score of 1 (almost perfect skin). 27. A method to treat a human patient suffering from vulgar pénfigo (PV) or foliaceous pénfigo (PF) that includes: manage a dose of 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenoxy-fenil) pyrazolo [3,4d] p¡r (PRN1008) Twice a day (IDB) for at least 14 days. 28. The method of modality 27, which also includes administering corticosteroid to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day). 29. The method of modality 27 or 28, where the dose of 400 mg IDB is administered for a maximum of 84 days. 30. The method of mode 27 or 28, where the dose of 400 mg IDB is administered for 14 days. 31. The method of modality 27 or 28, where the dose of 400 mg IDB is administered for 28 days. 32. The method of mode 27 or 28, which also includes the stepped increase in the dose of 400 mg IDB up to 500 mg IDB after a minimum of 14-28 days. 33. The method of modality 32, where the dose of 400 mg IDB is increasing staggered up to 500 mg bid after 33 days. 34. The method of mode 27 or 28, which also includes increasing the dose of 400 mg IDB up to 600 mg IDB after a minimum of 14-28 days. 35. The method of modality 34, where the dose of 400 mg IDB is increasing staggered up to 600 mg IDB after 22 days. Rozfrnn / ZZNZ / E / Yiai 36. The method of modality 34, where the dose of 400 mg IDB is increasing staggered up to 600 mg bid after 56 days. 37. The method of modality 32, which also includes increasing the dose of 500 mg IDB up to 600 mg bid after 14-28 days. 38. The method of any of the modalities 27 to 37, where before the administration of the dose of 400 mg IDB, the patient is maintained with a low dose of corticosteroid (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. 39. The method of any of the modalities 27 to 38, where before the administration of the dose of 400 mg bid, the patient has (a) without treating or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points. 40. The method of modality 28 or 39, where corticosteroid is prednisone, prednisolone, or methylprednisolone. 41. The method of any of the modalities 27-40, where PRN1008 includes a mixture of the isomers (e) and (z) of (r) -2- [3- [4-amino-3- (2-Fluoro-4-phenoxy-fenil) p¡razolo [3,4-d] pirim¡din-which Piperidin-1 -Carbonil] -4-methyl-4- [4- (oxetan-3-¡p ¡pezin-1 -Il] pent-2-enonitr¡lo. 42. The method of any of the modalities 27-41, where after the administration of PRN1008, the patient has a PDAI score of 1 (almost perfect skin). 43. A method to achieve a primary end point in 27 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceo pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenox Twice a day (IDB) for 14 days in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where before the administration of 400 mg IDB of PRN1008, the patient population has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. 44. A method to achieve a primary end point in 54 % of a population of human patients who is undergoing vulgar pénfigo (PV) or pénfigigo or foliage pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenox For 28 days in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where before the administration of 400 mg bid of PRN1008, the patient population has (a) without treating or recurrent PV; and (b) a cutaneous score of the Pénfigigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid to a Rozfrnn / ZZNZ / E / Yiai dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. 45. A method to achieve a primary end point in 54 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenox (IDB) for 28 days in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where before the administration of 400 mg IDB of PRN1008, the patient population has without treating or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. 46. ​​A method to achieve a primary end point in 73 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceo pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenox Days in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where before the administration of 400 mg IDB of PRN1008, the population of patients has unrelated or recurrent PV PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. 47. A method to achieve the complete remission of the disease in 17 % of a population of human patients who is undergoing vulgar pénfigo (PV) or pénfigigo or foliaceo pénfigo (PF) that includes administering to the population of patients 400 mg of (R) -2- [3- [4 am¡no-3- (2-fluoro-4-fenox¡-fen¡l) p¡razolo [3,4-d] p¡r¡m¡d¡n-1-¡¡piper¡d¡na-1-carbon¡l] -4-meth¡l-4- [4- (oxetan-3il) pipezin-1 (PRN1008) Twice a day (IDB) for 84 days, where before the administration of 400 mg IDB of PRN1008, the patient population has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. 48. A method to achieve the complete remission of the disease in 15 % to 17 % of Rozfrnn / ZZNZ / E / YIAI A population of human patients who is being subject to treatment for vulgar pénfigo (PV) or pénfigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2 [3- [4-am ¡no-3- (2-fluoro-4-phenoxy-fen¡l) pyrazolo [3,4-d] p¡r Twice a day (IDB) for 84 days, where before the administration of 400 mg IDB of PRN1008, the patient population has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 845 points, and is maintained with a low dose therapy of corticosteroid (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. 49. A method to achieve the complete remission of the disease in 25 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceo pénfigo (PF) that includes administering to the population of patients 400 mg of (R) -2- [3- [4 am¡no-3- (2-fluoro-4-fenox¡-fen¡l) p¡razolo [3,4-d] pir¡m¡d¡n-1-il] p¡per¡d¡na-1-carbon¡l] -4-meth¡l-4- [4- (oxetan-3il) piperaz (PRN1008) Twice a day (IDB) for 84 days, and subsequently subject the population of patients to follow -up for 84 days, during this follow -up, the population of PRN1008 patients or corticosteroid is not administered; where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 845 points, and is maintained with a low dose therapy of corticosteroid (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. 50. A method to obtain the complete remission of the disease in 23 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4 amino-3- (2-fluoro-4-phenoxi-phenyl) pyrazol days, and subsequently subject the population of patients to follow -up for 84 days, during this follow -up, the population of PRN1008 patients or corticosteroid is not administered; where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 845 points, and is maintained with a low dose therapy of corticosteroid (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. 51. A method of treating vulgar pénfigo (PV) or pénfigo or foliaceous pénfigo (PF) in a rozfrnn / zznz / e / yiai population of patients that includes the population will administer the population a dosing regime as follows: Administer (r) -2- [3- [4-amino-3- (2-Fluoro-4-phenoxy-fen¡l) p¡razolo [3,4-d] pirim¡d¡n-1-¡piperidin (PRN1008) at a starting dose of 400 mg IDB (in week 1) with a stepped increase adjustment of the intrapactive dose allowed up to 500 mg IDB or 600 mg IDB, where the dosing period ends in week 13; where the condition for the stepped increase in the dose is fine (a) The patient is not achieving control of the disease activity (CDA) or (b) is not reaching the end of the consolidation phase (ECP); where the control of the disease activity is defined as the visit in which the formation of new PV or PF injuries ceases and the established PV or PF lesions begin to be cured; where the end of the consolidation phase is defined as the visit in which new PV or PF injuries have not been developed for a minimum of 2 weeks and most of the established PV or PF lesions have been cured; where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. 52. The method of any of the modalities 43-51, where corticosteroid is prednisone, prednisolone, or methylprednisolone. 53. The method of any of the modalities 43-52, where PRN1008 includes a mixture of isomer (ξ) and (z) of (R) -2- [3- [4-am ¡no-3- (2-Fluoro-4-fenox Brief description of the drawings Fig. 1 represents the percentage of patients (n = 26) included in a phase 2 (part a) clinical trial in which 400 mg of PRN1008 IDB were administered with possible dose adjustment up to 600 mg of PRN1008 BID at the discretion of the researcher for a 12 -week treatment period that achieved control of the disease activity (CDA) at 2 weeks (27 %), 4 weeks (54 %) 12 weeks (73 %). A patient included in the part he abandoned on day 10 due to an adverse event not related to treatment (AE) was excluded from the analysis. Fig. 2 represents the control response rate of the disease activity ( %) on study day 15 (27 %), study day 29 (54 %), or study day 85 (73 %) for patients included in a phase 2 clinical trial (part a) in which 400 mg of PRN1008 ID with patients were administered with possible dose adjustment up to 600 mg of PRN1008 bid at the discretion of the researcher during A 12 -week treatment period. Error bars indicate a 95 %trust interval (IC). On study days 15 and 29, n = 26. On study day 85, n = 24. Rozfrnn / ZZNZ / E / Yiai Fig. 3 represents the percentage of patients (n = 24) included in a phase 2 (part a) clinical trial in which 400 mg of PRN1008 IDB were administered with possible dose adjustment up to 600 mg of PRN1008 BID at the discretion of the researcher for a 12 -week treatment period that achieved full remission (CR) at 12 weeks (17 %) and 24 weeks (25 %). Three patients included in Part A were excluded from the analysis due to an adverse event not related to treatment after 10, 43, and 44 days. Fig. 4 Represents PDAI scores (median (interruption range)) over time for patients included in a phase 2 clinical trial (part a) in which 400 mg of PRN1008 BID were administered with possible dose adjustment up to 600 mg of PRN1008 BID at the discretion of the researcher during a treatment period of 12 weeks. Fig. 5 represents PDAI scores (95 %average) over time for patients included in a phase 2 clinical trial (part a) in which 400 mg of PRN1008 ID with patients were administered with possible dose adjustment up to 600 mg of PRN1008 BID at the discretion of the researcher for a period of treatment of 12 weeks. Fig. 6 represents the percentage of patients (n = 14) included in a phase 2 clinical trial (part B) in which 400 mg of PRN1008 QD were administered during a 24 -week treatment period that achieved control of the disease activity (CDA) at 2 weeks (29 %), 4 weeks (43 %), and 12 weeks (50 %). A patient who passed from part B and started with 400 mg of PRN1008 BID was excluded from the analysis. Fig. 7 represents the percentage of patients (n = 15) included in a phase 2 clinical trial (part b) in which 400 mg of PRN1008 QD were administered with possible dose adjustment up to 600 mg of PRN1008 IDB at the discretion of the researcher for a 24 -week treatment period that achieved control of the disease activity (CDA) at 2 weeks (27 %), 4 weeks (53 %) 12 weeks (80 %). The patient who passed from part B and started with 400 mg of PRN1008 IDB was included in the analysis. Fig. 8a represents the percentage of patients (n = 15) included in a phase 2 clinical trial (part B) in which 400 mg of PRN1008 QD were administered with possible dose adjustment up to 600 mg of PRN1008 IDB at the discretion of the researcher for a 24 -week treatment period that managed to control the disease activity (CDA) at 4 weeks (60 %) and 12 weeks (87 %). The patient who passed from part B and started with 400 mg of PRN1008 IDB was included in the analysis. The error bars represent 80 % calculated by the Clopper Pearson method. Fig. 8B represents the percentage of patients (n = 14) included in a phase 2 clinical trial (part B) in which 400 mg of PRN1008 QD were administered during a 24 -week treatment period that managed to control the disease activity (CDA) at 4 weeks (50 %) and 12 weeks (50 %). The patient who passed from part B and started with 400 mg of PRN1008 BID was excluded from the analysis. The error bars represent 80 % calculated by Rozfrnn / ZZNZ / E / Yiai the Clopper Pearson method. Fig. 9A represents the percentage of patients (n = 14) included in a phase 2 clinical trial (part b) in which 400 mg of PRN1008 QD were administered with possible dose adjustment up to 600 mg of PRN1008 BID at the discretion of the researcher for a 24 -week treatment period that achieved complete remission (CR) at 12 weeks (13 %), 24 weeks (33 %), and 28 weeks weeks with treatment, 4 weeks without treatment) (40 %). The patient who passed from part B and started with 400 mg of PRN1008 IDB was included in the analysis. Fig. 9B represents the percentage of patients (n = 14) included in a phase 2 clinical trial (part B) in which 400 mg of PRN1008 QD were administered during a 24 -week treatment period that achieved full remission (CR) at 12 weeks (7 %), 24 weeks (7 %), and 28 weeks (24 weeks with treatment, 4 weeks without treatment) (7 %). The patient who passed from part B and started with 400 mg of PRN1008 BID was excluded from the analysis. Fig. 10 represents the average and medium of PDAI scores for patients (n = 16 over 8 weeks, n = 15 subsequently) included in a phase 2 clinical trial (part B) in which 400 mg of PRN1008 QD with possible dose adjustment up to 600 mg of PRN1008 BID at the discretion of the researcher for a 24 -week treatment period were administered to patients. A patient abandoned the study after 8 weeks due to a worsening of the pénfigo and was not included in the calculations of PDAI scores are 8 weeks. Fig. 11 represents the average and medium of the PDAI and average and medium scores of the use of corticosteroids (CS) for patients (n = 16 over 8 weeks, n = 15 subsequently) included in a phase 2 clinical trial (part B) in which 400 mg of PRN1008 QD were administered with possible dose adjustment up to 600 mg of PRN1008 BID to discretion during the researcher A 24 -week treatment period. A patient abandoned the study after 8 weeks due to a worsening of the pénfigo and was not included in the calculations of the PDAI / use of CS scores are 8 weeks. DEFINITIONS: Unless something else is affirmed, the following terms used in descriptive memory and claims are defined for the purposes of this application and have the following meanings. All the non -defined technical and scientific terms used in this application have the meaning that is commonly understood an expert in the technique to which this description belongs. As used in this memory, "a" or "one" entity refers to one or more of that entity; For example, a compound refers to one or more compounds or at least one compound unless something else is affirmed. As such, the terms "one" (or "one"), "one or more," and "at least one" can be used interchangeably in this memory. As used in this memory, the term "around" means approximately, in the region of, more or less, or near. When the term "around" is used jointly with a numerical range, it modifies that range extending the limits above and below the Rozfrnn / ZZNZ / E / Yiai numerical values. In general, the term "around" is used in this memory to modify a numerical value above and below the value indicated with a 5 %variance. With respect to specific values, it should be understood that the specific values ​​described in this Report for Populations of Subjects (eg, the subject of the clinical trial described) represent the median, medium, or statistical numbers, unless otherwise provided. Therefore, the aspects of this description that require a particular value in a subject are supported by this memory by the data of the population in which the relevant value is valued to be a significant delimitation of the population of subjects. As used in this memory, the term "active pharmaceutical ingredient" or "therapeutic agent" ("API") refers to a biologically active compound. As used in this memory, the terms "administer," "administering," or "administration" refer to this memory to provide, give, dose, and / or prescribe either by a healthcare professional or an authorized agent and / or introduce, take or consume by the patient or person by himself. For example, the "administration" of an API to a patient refers to any route (eg, oral administration) to introduce or administer the API to the patient. The administration includes self -administration and administration on the other. As used in this memory, the term “characterized by unrelated or recurrent pénfigo,” in reference to a human patient, refers to a human patient with freshly diagnosed or recurrent pénfigo, such as, p. eg, newly diagnosed or recurrent vulgar pénfigo or freshly diagnosed or recurrent foliaceous pénfigo. As a non -limiting example, "characterized by unrelated or recurrent pénfigo before the administration of PRN1008," in reference to a human patient, it refers to a human patient who has been recently diagnosed with a pénfigo or a human patient who suffers from recurrent pénfigo before starting a dosing regime that includes administering PRN1008. As used in this memory, the term “characterized by a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a corticosteroid,” in reference to a human patient, refers to a human patient to which a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) is administered corticosteroid, including patients who have not previously administered corticosteroids (0 mg / kg / day). As a non -limiting example, "characterized by a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a corticosteroid before the administration of PRN1008," in reference to a human patient, refers to a human patient without treatment with corticosteroids or a patient to whom a maintenance dose of less than or equal to 0.5 mg / kg / day (< 0.5 mg / kg / day) of a corticosteroid before starting a dosing regime that includes administering PRN1008 and optionally administer a corticosteroid, which can be the same or different from the corticosteroid used as a maintenance therapy before the administration of PRN1008 and can be administered to a dose or a dosing scheme that is the same or different from that used for maintenance therapy before maintenance therapy before PRN1008. Rozfrnn / ZZNZ / E / Yiai As used in this memory, unless otherwise specified, the term "complete remission" (CR) is defined as the absence of new and established injuries and it is intended to mean "absence of disease activity." As used in this memory, unless otherwise specified, the term “control of the disease activity” (CDA) (disease control) is defined as the visit in which the formation of new lesions of Pénfigigo ceases and the established pénfigo lesions begin to be cured. This is also considered the beginning of the consolidation phase. The expected time interval to achieve control of the disease activity is in the order of weeks, although it can be shorter. As used in this memory, unless otherwise specified, the term "final of the consolidation phase" (ECP) is defined as the visit in which new injuries have not been developed for a minimum of 2 weeks and the majority has been cured (eg at least 60 %, at least 70 %, at least 80 %) of the established lesions. Therefore, in order to get the ECP, the CDA must be confirmed in a visit> 2 weeks later and 80 % of the previously observed lesions must have been cured. As used in this memory, the term “after the administration of [x],” when it modifies a period of time, refers to a period of time that begins after the administration of [x] concludes. As a non -limiting example, "administer to the human patient a second dose of 400 mg of PRN1008 twice a day (IDB) for 14 days after the administration of the first dose" refers to begin the administration of the second dose after the administration of the first dose is completed and administer the second dose for 14 days, that is, yes, p. eg, the first dose was administered once a day on days 1 to 14, then the second dose will be administered twice a day in 15 to 28, for a period of total treatment of 28 days. As used in this memory, the term in combination with, when referring to two or more compounds, agents, or additional active pharmaceutical ingredients, means the administration of two or more compounds, agents, or active pharmaceutical ingredients to the patient before, concurrently with, or later one with respect to the other during a treatment period. Unless otherwise specified, the two or more compounds, agents, or active pharmaceutical ingredients can be administered in different schemes during the treatment period, such as, p. eg, administering one or more compounds, agents, or active pharmaceutical ingredients once a day and administering one or more compounds, agents, or active pharmaceutical ingredients twice a day. As used in this memory, an amount expressed in terms of “mg of [x]” refers to the total amount in milligrams of [x], that is, the free base. In some modalities, PRN1008 can be administered as a pharmaceutically acceptable salt of PRN1008, in which case an amount expressed in terms of “Mg of PRN1008” refers to the total amount in milligrams of PRN1008, that is, the free base, plus the equivalent amount of one or more pharmaceutically acceptable salts of PRN1008 on the basis of the base of the weight of the free base of the present memory. For example, “400 mg of at least one chosen compound from PRN1008 and pharmaceutically acceptable salts of it” includes 400 Rozfrnn / ZZNZ / E / Yiai Mg of PRN1008 and a concentration of one or more pharmaceutically acceptable salts of PRN1008 equivalent to 400 mg of PRN1008. As used in this memory, the term "Pénfigo injury" refers to an injury associated with or caused by Pénfigo, such as, p. eg, an injury associated with or caused by vulgar pénfigo or an injury associated with or caused by foliaceous pénfigo. As used in this memory, the term pharmaceutically acceptable salt refers to a salt form of an active pharmaceutical agent, where salt is not toxic. Pharmaceutically acceptable salts are well known in the technique and include those derived from adequate inorganic and organic acids. For example, S. M. Berge, et al. They describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19. As used in this memory, the term "PRN1008" refers to a compound that has the structure: Rozfrnn / ZZNZ / E / Yiai A dose of PRN1008 may contain the corresponding enantiomer (s) as an impurity in less than 1 % by weight or no more than approximately 5 % by weight. Similarly, a dose of the PRN1008 isomer (e) may contain the corresponding isomer (Z) as an impurity in less than 1 % by weight; A dose of PRN1008 isomer (Z) may contain the corresponding isomer (e) as an impurity in less than 1 % by weight. When PRN1008 is indicated as a mixture of isomers (e) and (z) of (R) -2- [3- [4-amino-3- (2fluoro-40 Isomer (e) or (z) in the mixture is greater than approximately 1 % by weight. In some modalities, the molar relationship of the isomer (e) A (Z) is 9: 1. PRN1008 or a pharmaceutically acceptable salt of it can also refer to this memory as a "drug," "active agent," "a therapeutically active agent," or "API." As used in this memory, the term "recurrence" is defined by the appearance of 3 or more new injuries in a month that do not cure spontaneously in 1 week, or by the extension of the established injuries, in a patient who has achieved control of the disease. As used in this memory, the term "treat," "treating," or "treatment," when used in connection with a disorder or condition, includes any effect, p. eg, decrease, reduce, modulate, improve, or eliminate, which results in the improvement of disorder or condition. The improvements of or the decrease in the severity of any symptoms of the disorder or condition can be easily assessed according to standard methods and techniques known in the technique. Some modalities of this description refer to methods to treat pénfigo in a human patient that needs it to understand the human patient a dose of at least 400 mg of (R) -2- [3- [4-am ¡no-3- (2-fluoro-4-fenox¡-fen¡l) p¡razolo [3,4-d] p¡r¡m¡din-1-il] piper¡d¡na-1-carbon¡l] -4mel Once a day (QD) for at least 14 days. In some modalities, a dose of at least 400 mg of PRN1008 QD for 14 to 168 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 QD for 14 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 QD for 28 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 QD for 84 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 QD for 168 days is administered to the human patient. In some modalities, the methods include administering the human patient a 400 mg dose of PRN1008 QD for at least 14 days. In some modalities, a dose of 400 mg of PRN1008 QD is given to the human patient for 14 to 168 days. In some modalities, a dose of 400 mg of PRN1008 QD for 14 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 QD for 28 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 QD for 84 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 QD for 168 days is administered to the human patient. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 once a day (QD) for 14 days; and administer to the human patient a second dose of 400 mg of PRN1008 twice a day (IDB) for at least 14 days after the administration of the first dose. In some modalities, a second dose of 400 mg of PRN1008 IDB for 14 to 154 days after the administration of the first dose is administered to the human patient. In some modalities, PRN1008 is administered to the human patient for a maximum of 168 days. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 once a day (QD) for 14 days; and administer to the human patient a second dose of 400 mg of PRN1008 twice a day (IDB) for 14 days after the administration of the first dose; and administer to the human patient a third dose of 600 mg of PRN1008 twice a day (IDB) Rozfrnn / ZZNZ / E / YIAI 2- [3- [4-am ¡no-3- (2-Fluoro-4-fenox¡-phenyl) pyrazolo [3,4-d] pir¡midin-1 -Il] Piperidin-1 -Carbonil] -4-methyl-4- [4 (oxetan-3-il) piperaz¡n-1-¡pent-2-enonitr¡lo. In some modalities, the methods include treating vulgar pénfigo. In some modalities, the methods include treating foliaceous pénfigo. In some modalities, the methods include reducing a skin score of the index of the Pénfigo disease activity (PDAI). In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 20 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 25 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 30 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 35 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 40 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 45 %. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 50 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 55 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 60 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo (PDAI) disease activity index at least 65 %. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 70 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 75 %. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 80 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 85 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 90 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) activity after 14 days of the administration of PRN1008. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index after 28 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index after 56 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index after 84 days of the administration of PRN1008. In some modalities, the methods include reducing a skin score of the Rozfrnn / ZZNZ / E / Yiai Pénfigigo disease (PDAI) activity after 112 days of the PRN1008 administration. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) activity after 140 days of the PRN1008 administration. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index after 168 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 20 % after 14 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 20 % after 28 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 50 % after 56 days of the PRN administration. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 50 % after 84 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 70 % after 168 days of the PRN administration. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 75 % after 168 days of the PRN1008 administration. In some modalities, the human patient is characterized by a skin score of the Pénfigo (PDAI) disease activity index of 0 or 1 after the PRN1008 administration. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo disease activity (PDAI) index of 0 after the administration of PRN1008. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo disease activity (PDAI) activity of 1 after the administration of PRN1008. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo (PDAI) disease activity of 0 or 1 after 168 days of the PRN1008 administration. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo disease activity (PDAI) index of 0 after 168 days of the PRN1008 administration. In some modalities, the human patient is characterized by a skin score of the Pénfigo disease activity (PDAI) index of 1 after 168 days of the PRN1008 administration. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 20 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 25 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 30 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 35 %. Rozfrnn / ZZNZ / E / Yiai In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 40 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 45 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 50 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 55 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 60 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 65 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 20 % after 56 days of the administration of PRN1008. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 30 % after 84 days of the administration of PRN1008. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 50 % after 112 days of the administration of PRN1008. In some modalities, the methods include achieving a complete remission. In some modalities, the methods include achieving complete remission after 84 days of the administration of PRN1008. In some modalities, the methods include achieving complete remission after 168 days of the administration of PRN1008. In some modalities, the methods include obtaining control of the activity of the disease defined as a visit for a medical checkup in which the formation of new pénfigo injuries ceases and the established pénfigo lesions begin to be cured. In some modalities, the methods include achieving control of the disease activity after 84 days of the administration of PRN1008. In some modalities, the methods include achieving control of the activity of the disease after 168 days of the administration of PRN1008. In some modalities, the methods include healing established pénfigo injuries. In some modalities, the methods include healing at least 50 % of established pénfigo lesions. In some modalities, the methods include healing at least 60 % of established pénfigo lesions. In some modalities, the methods include healing at least 70 % of established pénfigo lesions. In some modalities, the methods include healing at least 80 % of established pénfigo lesions. In some modalities, the methods include healing at least 90 % of established pénfigo lesions. In some modalities, the methods include healing at least 50 % of established Pénfigo lesions after 84 days of the PRN1008 administration. In some modalities, the methods include healing at least 60 % of established Pénfigo lesions after 84 days of the PRN1008 administration. In some modalities, the methods include healing at least 70 % of established Pénfigo lesions after 84 days of the PRN1008 administration. In Rozfrnn / ZZNZ / E / Yiai some modalities, the methods include healing at least 80 % of established pénfigo lesions after 84 days of the PRN1008 administration. In some modalities, the methods include healing at least 90 % of established Pénfigo lesions after 84 days of the PRN1008 administration. Rozfrnn / ZZNZ / E / Yiai In some modalities, the methods include healing at least 50 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include healing at least 60 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include healing at least 70 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include healing at least 80 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include healing at least 90 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include preventing the formation of new pénfigo injuries. In some modalities, the methods include preventing the formation of new pénfigo injuries after 84 days of the administration of PRN1008. In some modalities, the methods include preventing the formation of new pénfigo injuries after 168 days of the administration of PRN1008. In some modalities, the methods include achieving the end of the consolidation phase defined as a medical visit in which new pénfigo injuries have not been developed for a minimum of 2 weeks and most of the established Pénfigo lesions have been cured. In some modalities, more than the established pénfigo lesions have been cured. In some modalities, more than the established pénfigo lesions have been cured. In some modalities, more than the established pénfigo lesions have been cured. In some modalities, more than the established pénfigo lesions have been cured. In some modalities, more than 90 % of established Pénfigo lesions have been cured. In some modalities, the methods include achieving the end of the consolidation phase defined as a medical visit in which new pénfigo injuries have not been developed for a minimum of 2 weeks and most of the established Pénfigo lesions have been cured after 168 days of the PRN1008 administration. In some modalities, more than 50 % of established pénfigo lesions have been cured. In some modalities, more than 60 % of established Pénfigo lesions have been cured. In some modalities, more than 70 % of established pénfigo lesions have been cured. In some modalities, more than 80 % of established pénfigo lesions have been cured. In some modalities, more than 90 % of established Pénfigo lesions have been cured. This memory also describes methods to treat a human patient who suffers from vulgar pénfigo or foliaceous pénfigo that understand the human patient a dose of 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenoxi-fen¡l) pyrazolo [3,4-d] pirim¡din-1-il] p¡peridine-1-carbonil] -4metil-4- [4- (oxetan-3-il) pent At least days. In some modalities, a dose of 400 mg of PRN1008 QD is given to the human patient for 14 to 168 days. In some modalities, a dose of 400 mg of PRN1008 QD is given to the human patient for a maximum of 168 days. In some modalities, a dose of 400 mg of PRN1008 QD for 14 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 QD is given to the patient for 28 days. In some modalities, a dose of 400 mg of PRN1008 QD for 84 days is administered to the patient. In some modalities, a dose of 400 mg of PRN1008 QD for 168 days is administered to the patient. Some modalities of this description refer to methods to treat pénfigo in a human patient that needs it to understand the human patient a dose of at least 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenoxy-fen¡l) p¡razolo [3,4-d] pirimid¡n-1-¡¡piperidin-1-carbonil] -4metil-4- [4- (oxetan-3-il) piperaz (IDB) for at least 14 days. In some modalities, a dose of at least 400 mg of PRN1008 IDB for 14 to 84 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 IDB for 14 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 IDB for 28 days is administered to the human patient. In some modalities, a dose of at least 400 mg of PRN1008 IDB for 84 days is administered to the human patient. In some modalities, the methods include managing the human patient a dose of 400 mg of PRN1008 IDB for at least 14 days. In some modalities, a dose of 400 mg of PRN1008 BID for 14 to 84 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 BID for 14 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 BID for 28 days is administered to the human patient. In some modalities, a dose of 400 mg of PRN1008 BID for 84 days is administered to the human patient. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 twice a day (IDB) for at least 14 days; and administer to the human patient a second dose of 500 mg of PRN1008 twice a day (IDB) after the administration of the first dose. In some modalities, a first dose of 400 mg of PRN1008 IDB for 14 to 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for more than 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for 33 days is administered to the human patient. In some modalities, PRN1008 is administered to the human patient for a maximum of 84 days. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 twice a day (IDB) for at least 14 days; and administer to the human patient a second dose of 600 mg of PRN1008 twice a day (IDB) after the administration of the first dose. In some modalities, a first dose of 400 mg of PRN1008 IDB for 14 to 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for more than 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for 22 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for 56 days is administered to the human patient. In some modalities, PRN1008 is administered to the human patient for a maximum of 84 days. In some modalities, the methods include: Administer to the human patient a first dose of 400 mg of PRN1008 twice a day (IDB) for at least 14 days; Administer to the human patient a second dose of 500 mg of PRN1008 twice a day (IDB) for at least 14 days after the administration of the first dose; and administer to the human patient a third dose of 600 mg of PRN1008 twice a day (IDB) after the administration of the second dose. In some modalities, a first dose of 400 mg of PRN1008 IDB for 14 to 28 days is administered to the human patient. In some modalities, a first dose of 400 mg of PRN1008 BID for more than 28 days is administered to the human patient. In some modalities, a second dose of 500 mg of PRN1008 IDB for 14 to 28 days after the administration of the first dose is administered to the human patient. In some modalities, PRN1008 is administered to the human patient for a maximum of 84 days. In some modalities, the methods include administering PRN1008 in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day). In some modalities, the first corticosteroid is chosen from prednisone, prednisolone, and methylprednisolone. In some modalities, the human patient is characterized by unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by non -treating Pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by vulgar unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by non -treating vulgar pénfigo before the administration of PRN1008. In some modalities, Rozfrnn / ZZNZ / E / Yiai The human patient is characterized by recurrent vulgar pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by unrelated or recurrent foliaceous pénfigo before the PRN1008 administration. In some modalities, the human patient is characterized by non -treated foliaceous pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by recurrent foliaceous pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo (PDAI) disease activity from 8 points to 60 points before the PRN1008 administration. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo (PDAI) disease activity from 8 points to 45 points before the PRN1008 administration. In some modalities, the human patient is characterized by a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid before the administration of PRN1008. In some modalities, the second corticosteroid is chosen from prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid is the same as the second corticosteroid. In some modalities, the first corticosteroid is not the same as the second corticosteroid. In some modalities, PRN1008 includes the isomer (e) of (R) -2- [3- [4-amino-3- (2-fluoro-4Fenox¡-fenil) p¡razolo [3,4-d] p¡r In some modalities, PRN1008 includes the isomer (Z) of (R) -2- [3- [4-amino-3- (2-Floro4-fenox¡-fen¡l) p¡razolo [3,4-d] p¡r¡m¡d¡n-1-¡l] p¡p Er¡d¡na-1-carbon¡l] -4-meth¡l-4- [4- (oxetan-3-¡¡p¡peraz¡n-1-¡l] pent2-enonitrile. In some modalities, PRN1008 includes a mixture of isomers (e) and (z) of (R) 2- [3- [4-Am¡no-3- (2-Flore-4-fenox Er¡d¡na-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-¡¡¡¡¡¡¡¡¡ In some modalities, the methods include reducing a skin score of the index of the Pénfigo disease activity (PDAI). In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 20 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 25 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 30 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 35 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 40 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 45 %. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 50 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 55 %. In some Rozfrnn / ZZNZ / E / Yiai Modalities, the methods include reducing a cutaneous score of the Pénfigigo disease activity index (PDAI) at least 60 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo (PDAI) disease activity index at least 65 %. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 70 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 75 %. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 80 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 85 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 90 %. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) activity after 14 days of the administration of PRN1008. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index after 28 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index after 56 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index after 84 days of the administration of PRN1008. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index after 112 days of the PRN1008 administration. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) activity after 140 days of the PRN1008 administration. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index after 168 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 20 % after 14 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 20 % after 28 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 50 % after 56 days of the PRN administration. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 50 % after 84 days of the PRN1008 administration. In some modalities, the methods include reducing a cutaneous score of the Pénfigo disease activity (PDAI) index at least 70 % after 168 days of the PRN administration. In some modalities, the methods include reducing a skin score of the Pénfigo disease activity (PDAI) index at least 75 % after 168 days of the PRN1008 administration. Rozfrnn / ZZNZ / E / Yiai In some modalities, the human patient is characterized by a skin score of the Pénfigo (PDAI) disease activity index of 0 or 1 after the PRN1008 administration. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo disease activity (PDAI) index of 0 after the administration of PRN1008. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo disease activity (PDAI) activity of 1 after the administration of PRN1008. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo (PDAI) disease activity of 0 or 1 after 168 days of the PRN1008 administration. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo disease activity (PDAI) index of 0 after 168 days of the PRN1008 administration. In some modalities, the human patient is characterized by a skin score of the Pénfigo disease activity (PDAI) index of 1 after 168 days of the PRN1008 administration. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 20 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 25 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 30 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 35 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 40 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 45 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 50 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 55 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 60 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 65 %. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 20 % after 56 days of the administration of PRN1008. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 30 % after 84 days of the administration of PRN1008. In some modalities, the methods include reducing the average daily use of corticosteroids by the human patient at least 50 % after 112 days of the administration of PRN1008. In some modalities, the methods include achieving a complete remission. In some modalities, the methods include achieving complete remission after 84 days of the Rozfrnn / ZZNZ / E / Yiai Administration of PRN1008. In some modalities, the methods include achieving complete remission after 168 days of the administration of PRN1008. In some modalities, the methods include obtaining control of the activity of the disease defined as a visit for a medical checkup in which the formation of new pénfigo injuries ceases and the established pénfigo lesions begin to be cured. In some modalities, the methods include achieving control of the disease activity after 84 days of the administration of PRN1008. In some modalities, the methods include achieving control of the activity of the disease after 168 days of the administration of PRN1008. In some modalities, the methods include healing established pénfigo injuries. In some modalities, the methods include healing at least 50 % of established pénfigo lesions. In some modalities, the methods include healing at least 60 % of established pénfigo lesions. In some modalities, the methods include healing at least 70 % of established pénfigo lesions. In some modalities, the methods include healing at least 80 % of established pénfigo lesions. In some modalities, the methods include healing at least 90 % of established pénfigo lesions. In some modalities, the methods include healing at least 50 % of established Pénfigo lesions after 84 days of the PRN1008 administration. In some modalities, the methods include healing at least 60 % of established Pénfigo lesions after 84 days of the PRN1008 administration. In some modalities, the methods include healing at least 70 % of established Pénfigo lesions after 84 days of the PRN1008 administration. In some modalities, the methods include healing at least 80 % of established Pénfigo lesions after 84 days of the PRN1008 administration. In some modalities, the methods include healing at least 90 % of established Pénfigo lesions after 84 days of the PRN1008 administration. In some modalities, the methods include healing at least 50 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include healing at least 60 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include healing at least 70 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include healing at least 80 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include healing at least 90 % of established Pénfigo lesions after 168 days of the PRN1008 administration. In some modalities, the methods include preventing the formation of new pénfigo injuries. In some modalities, the methods include preventing the formation of new pénfigo injuries after 84 days of the administration of PRN1008. In some modalities, the methods include preventing the formation of new pénfigo injuries after 168 days of the administration of PRN1008. Pozfrnn / ZZNZ / E / Yiai In some modalities, the methods include achieving the end of the consolidation phase defined as a medical visit in which new pénfigo injuries have not been developed for a minimum of 2 weeks and most of the established Pénfigo lesions have been cured. In some Rozfrnn / ZZNZ / E / Yiai Modalities, more than the established Pénfigo lesions have been cured. In some modalities, more than the established pénfigo lesions have been cured. In some modalities, more than the established pénfigo lesions have been cured. In some modalities, more than the established pénfigo lesions have been cured. In some modalities, more than 90 % of established Pénfigo lesions have been cured. In some modalities, the methods include achieving the end of the consolidation phase defined as a medical visit in which new pénfigo injuries have not been developed for a minimum of 2 weeks and most of the established Pénfigo lesions have been cured after 168 days of the PRN1008 administration. In some modalities, more than 50 % of established pénfigo lesions have been cured. In some modalities, more than 60 % of established Pénfigo lesions have been cured. In some modalities, more than 70 % of established pénfigo lesions have been cured. In some modalities, more than 80 % of established pénfigo lesions have been cured. In some modalities, more than 90 % of established Pénfigo lesions have been cured. Some modalities of this description refer to methods to achieve a primary end point in 17 % to 39 % of a population of human patients who are being subjected to treatment for pénfigo that understand: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-Am¡no-3- (2-Fluoro-4-fenox Er¡d¡na-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-¡¡¡¡¡¡¡¡¡ (PRN1008) Once a day (QD) for 14 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where each member of the population of human patients was characterized by: without treating or recurrent pénfigo; and a cutaneous score of the Pénfigigo (PDAI) disease activity of 8-60 points, a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the primary final point comprises the control of the disease activity (CDA) defined as a visit for a visit for a visit for a visit for a visit for a visit for a visit for the which ceases the formation of new pénfigo injuries and the established pénfigo lesions begin to be cured. In some modalities, the methods include getting the primary end point in 22 % to 34 % of the population of human patients. In some modalities, the methods include getting the primary end point in 27 % to 29 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method is also provided to achieve a primary end point in 27 % to 29 % of a population of human patients who are undergoing treatment for vulgar pénfigo (PV), pénfigigo, or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2 [3- [4-amino-3- (2-fluoro-4-phenoxy-fenil) pyrazol days in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where before the administration of 400 mg QD of PRN1008, the patient population has unrelated or recurrent PV PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 860 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. Some modalities of this description refer to methods to achieve a primary end point in 33 % to 53 % of a population of human patients who are undergoing treatment for pénfigo that understand: Administer to each member of the human patient population a dose of 400 mg of (r) -2 [3- [4-am -Carbonil] -4-methyl-4- [4 (oxetan-3-¡¡pc) Human patients were characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, rozfrnn / zznz / e / yiai before the administration of PRN1008, where the primary final point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new injuries in which the formation of new injuries ceases The established pénfigo lesions begin to be cured. In some modalities, the methods include achieving the primary end point in 38 % to 48 % of the population of human patients. In some modalities, the methods include getting the primary end point in 43 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. In this memory, a method to achieve a primary end point is also provided in 43 % of a population of human patients who are undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-am ¡no-3- (2-Flore-4-phenoxy-fenil) Pyrazolo [3,4-d] Pirimidin-1-il] p¡per¡dina-1-carbonil] -4-meth¡l4- [4- (oxetan-3-il) piperazin-1-il] pent-2-initrile (PRN1008) once (QD) for 28 days, where the population of patients is also administered to the population of PRN1008, a corticosteroid population is also administered at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. Some modalities of this description refer to methods to achieve a primary end point in 40 % to 60 % of a population of human patients who are being subjected to Rozfrnn / ZZNZ / E / YIAI Treatment for Pénfigo that they understand: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-Am¡no-3- (2-Flore-4-fenoxi-fen¡l) P¡razolo [3,4-d] p¡rim¡d¡n-1-¡l] p¡per¡dina-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-¡l) p¡perazin-1 (PRN1008) Once a day (QD) for 84 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where each member of the population of human patients was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the primary final point includes the control of the disease activity (CDA) defined as a visit for a medical check -in Pénfigo In some modalities, the methods include achieving the primary end point in 45 % to 55 % of the population of human patients. In some modalities, the methods include getting the primary end point in 50 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. In this memory, a method to achieve a primary end point is also provided in 50 % of a population of human patients who are undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-Am¡no-3- (2-Fluoro-4-fenox (PRN1008) Once a day (QD) for 84 days, where Rozfrnn / ZZNZ / E / YIAI throughout the administration of PRN1008 to the patient population, also administered to the population of patients a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a medical check -up visit in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. Some modalities of this description refer to methods to achieve a primary end point in 43 % to 63 % of a population of human patients who are being subjected to treatment for pénfigo that includes: Administer to each patient population member a 400 mg dose of (r) -2- [3- [4 amino-3- (2-fluoro-4-phenoxy-phenyl) p¡razolo [3,4-d] p¡rimidin-1-¡piperidin -Il] Pent-2-initr¡lo (PRN1008) once a day (QD) for 14 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), followed by a dose of 400 mg of PRN100 A dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where each member of the human patient population was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the primary final point includes the control of the disease activity (CDA) defined as a visit for a medical check -in Pénfigo In some modalities, the methods include achieving the primary end point in 48 % to 58 % of the population of human patients. In some modalities, the methods include getting the primary end point in 53 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent before the administration of PRN1008. Rozfrnn / ZZNZ / E / Yiai In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method to achieve a primary end point is also included in 53 % of a population of human patients who are undergoing vulgar pénfigo (PV) or Pénfigigo or Foliaceous Pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2fluoro-4-fenoxi-fen¡l) p¡razolo [3,4-d] p¡rimidin-1-¡l] p¡per¡d¡na-1-carbon¡l] -4-meth¡l-4- [4- (oxetan-3-¡l) pieraz Once a day (QD) for 14 days, followed by the staggered increase in the PRN1008 dose up to 400 mg IDB for 14 days, where the population of patients throughout the PRN1008 administration is also administered to the population of patients a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a visit for a medical checkup in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. Some modalities of this description refer to methods to achieve a primary end point in 70 % to 90 % of a population of human patients who are being subject to treatment for pénfigo that comprise: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-am ¡no-3- (2-fluoro-40 Day (QD) for 14 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), followed by a dose of 400 mg of PRN1008 twice a day (IDB) for 14 days in combination with the first corticosteroid at a dose of less than or equal to 0.5 mg / kg / kg / day 0.5 mg / kg / day), followed in addition to a dose of 600 mg of PRN1008 twice a day (IDB) for 56 days in combination with the first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where each member of the human patient population was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points; and rozfrnn / zznz / e / yiai a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the primary final point includes the control of the disease activity (CDA) defined as a visit for a medical check -in and the established pénfigo lesions begin to be cured. In some modalities, the methods include getting the primary end point in 75 % to 85 % of the population of human patients. In some modalities, the methods include getting the primary end point in 80 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method to achieve a primary end point is also included in 80 % of a population of human patients who are undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceo pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2fluoro-4-phenoxi-fen¡l) pyrazol Days, followed by the staggered increase in the dose of PRN1008 to 400 mg IDB for 14 days, in addition to the staggered increase in the DOS 0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a visit for a medical checkup in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. Rozfrnn / ZZNZ / E / Yiai Some modalities of this description refer to methods to achieve the complete remission of the disease in 4.5 % to 9.5 % of a population of human patients who are being subject to treatment for pénfigo that comprise: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-amino-3- (2-fluoro-4-fenoxi-fen¡l) p¡razolo [3,4-d] p¡rim¡d¡n-1-¡¡¡l] p¡per¡d¡na-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-¡l) piperaz (PRN1008) Once a day (QD) for 84 days, where each member of the human patient population was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a first corticosteroid, before the administration of PRN1008, where the complete remission is defined as the absence of new and established lesions of Pénfigo. In some modalities, the methods include achieving the complete remission of the disease in 6 % to 8 % of the population of human patients. In some modalities, the methods include achieving the complete remission of the disease in 7 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, the methods include administering a dose of 400 mg of (r) -2- [3- [4-amino-3- (2-fluoro-4-phenoxy-fenyl) pyrazolo [3,4d] pyrimidin-1 -Il] piperid¡na-1 -Carbonil] -4-meth¡l-4- [4- (oxetan-3-il) piperaz¡n-1 -Il] Pent-2-initrile (PRN1008) Once a day (QD) for 84 days in combination with a second corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day). In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. Rozfrnn / ZZNZ / E / Yiai A method is also provided to obtain the complete remission of the disease in 7 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering to the population of patients 400 mg of (R) -2- [3- [4-am ¡no-3- (2-Fluoro-4-fenox per¡d¡na-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-¡¡¡¡¡¡¡¡¡ (PRN1008) Once a day (QD) for 84 days, where before the administration of 400 mg QD of PRN1008, the patient population has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 860 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. In some modalities, PRN1008 is administered in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day). Some modalities of this description refer to methods to achieve the complete remission of the disease in 3 % to 23 % of a population of human patients who are being subject to treatment for pénfigo that they understand: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-amino-3- (2-fluoro-4-phenoxy-fen¡l) pyrazol Day (QD) for 14 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), followed by a dose of 400 mg of PRN1008 twice a day (IDB) for 14 days in combination with the first corticosteroid at a dose of less than or equal to 0.5 mg / kg / kg / day 0.5 mg / kg / day), followed in addition to a dose of 600 mg of PRN1008 twice a day (IDB) for 56 days in combination with the first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where each member of the human patient population was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the complete remission is defined as the absence of new and established pénfigo lesions. In some modalities, the methods include achieving the complete remission of the disease in 8 % to 18 % of the population of human patients. In some modalities, the methods include achieving the complete remission of the disease in 13 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. Rozfrnn / ZZNZ / E / Yiai In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method is also provided to achieve the complete remission of the disease in 13 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigo or foliaceous pénfigo (PF) that includes administering to the population of patients 400 mg of (R) -2- [3- [4-Am¡no-3- (2-Flore-4-fenoxi-fen¡l) p¡razolo [3,4-d] p¡r¡m¡d¡n-1-¡l] p¡per¡dina-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-il) pent (PRN1008) Once a day (QD) for 14 days, followed by the staggered increase in the dose of PRN1008 to 400 mg IDB for 14 days, followed by the additional staggered increase of the dose up to 600 mg IDB for 56 days, where throughout the administration of PRN1008 to the population of patients, the population is also administered to the population of patients a corticosteroid at a dose of or equal to a dose of or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. Some modalities of this description refer to methods to achieve the complete remission of the disease in 30 % to 50 % of a population of human patients who are being subject to treatment for pénfigo that they understand: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-amino-3- (2-fluoro-4-phenoxi-fen¡l) pyrazolo [3,4-d] pirim¡d¡n-1-il] piperid¡na-1-carbonil] -4-meth¡l-4- [4 (oxetan-3-¡l) piperaz A day (QD) for 14 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), followed by a dose of 400 mg of PRN1008 twice a day (IDB) for 14 days in combination with the first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day 0.5 mg / kg / day), followed in addition to a dose of 600 mg of PRN1008 twice a day (IDB) for 140 days in combination with the first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); and Rozfrnn / ZZNZ / E / Yiai Submit each member of the population of human patients to a post -treatment period of 28 days after the administration of PRN1008 during which PRN1008 or corticosteroid is not administered, where each member of the human patient population was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the complete remission is defined as the absence of new and established pénfigo lesions. In some modalities, the methods include achieving the complete remission of the disease in 35 % to 45 % of the population of human patients. In some modalities, the methods include achieving the complete remission of the disease in 40 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method is also provided to obtain the complete remission of the disease in 40 % of a population of human patients who is undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering to the population of patients 400 mg of (R) -2- [3- [4-Am¡no-3- (2-Flore-4-fenoxi-fen¡l) p¡razolo [3,4-d] p¡r¡m¡d¡n-1-¡l] p¡per¡dina-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-il) pent (PRN1008) Once a day (QD) for 14 days, followed by the staggered increase in the DOS dose of PRN1008 to 400 mg IDB for 14 days, followed by the additional stepped increase of the dose up to 600 mg IDB for 140 days, and subsequently submit the population of patients to follow -up for 28 days, during said monitoring, the population of patients PRN1008 or corticosteroid is not administered; where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, Rozfrnn / ZZNZ / E / Yiai and is maintained with a low dose therapy of corticosteroid (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. Some modalities of this description refer to methods to treat pénfigo in a human patient that understand: Administer to the human patient a dose of 400 mg of (r) -2- [3- [4-amino-3- (2-fluoro-4-phenox (PRN1008) Once a day, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); Assess whether the human patient is getting control of the disease activity and / or is reaching the end of the consolidation period during week 3 and increasing the Dose of PRN1008 up to 400 mg IDB if the human patient is not getting control of the disease activity and / or is not reaching the end of the consolidation period during week 3; Value whether the human patient is getting control of the disease activity and / or is reaching the end of the consolidation period during week 5 and increasing the dose of PRN1008 up to 600 mg bid if the human patient is not getting control of the disease activity and / or is not reaching the end of the consolidation period during week 5, where: The control of the disease activity (CDA) is defined as a visit for a medical checkup in which the formation of new pénfigo injuries ceases and the established pénfigo lesions begin to be cured; The end of the consolidation phase is defined as a medical visit in which new pénfigo injuries have not been developed for a minimum of 2 weeks and most of the established Pénfigo lesions have been cured. In some modalities, the human patient is characterized by unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by vulgar unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by unrelated or recurrent foliaceous pénfigo before the PRN1008 administration. In some modalities, the human patient is characterized by a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points before the PRN1008 administration. In some modalities, the human patient is characterized by a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid before the administration of PRN1008. In some modalities, the human patient is characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points; and Rozfrnn / ZZNZ / E / YIAI A maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, PRN1008 is administered to the patient for 25 weeks. In some modalities, the end of the consolidation phase is defined as a medical visit in which new pénfigo injuries have not been developed for a minimum of 2 weeks and at least 50 % of the established Pénfigo lesions have been cured. In some modalities, the end of the consolidation phase is defined as a medical visit in which new pénfigo injuries have been developed for a minimum of 2 weeks and at least 60 % of the established Pénfigo lesions have been cured. In some modalities, the end of the consolidation phase is defined as a medical visit in which new pénfigo injuries have been developed for a minimum of 2 weeks and at least 70 % of the established Pénfigo lesions have been cured. In some modalities, the end of the consolidation phase is defined as a medical visit in which new pénfigo injuries have not been developed for a minimum of 2 weeks and at least 80 % of the established Pénfigo lesions have been cured. In some modalities, the end of the consolidation phase is defined as a medical visit in which new pénfigo injuries have not been developed for a minimum of 2 weeks and at least 90 % of the established Pénfigo lesions have been cured. A method to treat vulgar pénfigo (PV) or pénfigo or foliage pénfigo (PF) is also provided in a population of patients that includes administering a dosing regime to the population as follows: Administer (r) -2- [3- [4-Am¡no-3- (2-Fluoro-4-fenoxi-fen¡l) p¡razolo [3,4-d] pirim¡d¡n-1-¡l] p¡perid¡na-1carbonil] -4-methyl-4- [4- (oxetan-3-il) p¡peraz¡n-1-¡ (PRN1008) at a starting dose of 400 mg QD (in week 1) with a stepped increase in the permitted dose in week 3 to 400 mg IDB and in week 5 to 600 mg IDB, where the dosing period ends in week 25; where the condition for the stepped increase in the dose is fine (a) The patient is not achieving control of the disease activity (CDA) or (b) is not reaching the end of the consolidation phase (ECP); where the control of the disease activity is defined as the visit in which the formation of new PV or PF injuries ceases and the established PV or PF lesions begin to be cured; where the end of the consolidation phase is defined as the visit in which they have not been rozfrnn / zznz / e / yiai developed new PV or PF injuries for a minimum of 2 weeks and most of the established PV or PF lesions have been cured; where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. Some modalities of this description refer to methods to treat pénfigo in a human patient that include administering the human patient a dose of 400 mg of (R) -2- [3- [4 am¡no-3- (2-fluoro-4-phenox¡-phenyl) p¡razolo [3,4-d] p¡r¡midin-1-piper¡d¡na-1-carbon¡l] -4-methyl-4- [4- (oxetan-3il) pipezin-1 A day (IDB) for 168 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day). In some modalities, the human patient is characterized by: without treating or recurrent pénfigo; and a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008. In some modalities, the methods include treating vulgar pénfigo. In some modalities, the methods include treating foliaceous pénfigo. In some modalities, the human patient is characterized by vulgar unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the human patient is characterized by unrelated or recurrent foliaceous pénfigo before the PRN1008 administration. In some modalities, the methods include treating vulgar pénfigo and the human patient is characterized by vulgar unrelated or recurrent pénfigo before the administration of PRN1008. In some modalities, the methods include treating foliaceous pénfigo and the human patient is characterized by unrelated or recurrent foliaceous pénfigo before the administration of PRN1008. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method to treat a human patient who suffers from vulgar pénfigo Rozfrnn / ZZNZ / E / Yiai (PV) or foliage pénfigo (PF) that includes: Administer to the patient a dose of 400 mg of (r) -2- [3- [4-amino-3- (2-fluoro-4-phenox¡phenyl) pyrazolo [3,4-d] pirimidin-1 -Il] piperidine-1 -Carbonil] -4-methyl-4- [4- (oxetan-3-il) piperaz (PRN1008) Twice a day (IDB) for 168 days, where throughout the administration of PRN1008, a corticosteroid is also given to the patient at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg IDB of PRN1008, the patient has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. This description also provides a method to treat a human patient suffering from vulgar pénfigo (PV) or foliaceous pénfigo (PF) that includes: Administer a dose of 400 mg of (r) -2- [3- [4-amino-3- (2-fluoro-4-phenoxy-fen¡l) p¡razolo [3.4d] pirimidin-1 -Il] Piperidin-1 -Carbonil] -4-methyl-4- [4- (oxetan-3-¡l) Pipe. (PRN1008) Twice a day (IDB) for at least 14 days. Some modalities of this description refer to methods to achieve a primary end point in 17 % to 37 % of a population of human patients who are undergoing treatment for pénfigo that comprise: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-Am¡no-3- (2-Flore-4-fenoxi-fen¡l) p¡razolo [3,4-d] p¡rim¡d¡n-1-¡l] p¡per¡d¡na-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-¡l) Pipe (PRN1008) Twice a day (IDB) for 14 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where each member of the population of human patients was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the primary final point includes the control of the disease activity (CDA) defined as a visit for a medical check -in Pénfigo In some modalities, the methods include achieving the complete remission of the disease in 22 % to 32 % of the population of human patients. In some modalities, the methods include achieving the complete remission of the disease in 27 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. Rozfrnn / ZZNZ / E / Yiai In some modalities, each member of the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method is also provided to achieve a primary end point in 27 % of a population of human patients who are undergoing vulgar pénfigo (PV) or pénfigigo or foliaceo pénfigo (PF) that includes administering to the population of patients 400 mg of In (IDB) for 14 days in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where before the administration of 400 mg IDB of PRN1008, the patient population has without treating or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a visit for a medical checkup in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. Some modalities of this description refer to methods to achieve a primary end point in 44 % to 64 % of a population of human patients who are being subject to treatment for pénfigo that comprise: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-Am¡no-3- (2-Flore-4-phenoxi-fen¡l) Pyrazolo [3,4-d] pirim¡d¡n-1-¡l] p¡per¡d¡na-1-carbonil] -4-meth¡l-4- [4 (oxetan-3-¡¡pc) pipe times a day (IDB) for 28 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where each member of the population of human patients was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points; and rozfrnn / zznz / e / yiai a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the primary final point includes the control of the disease activity (CDA) defined as a visit for a medical check -in and the established pénfigo lesions begin to be cured. In some modalities, the methods include achieving the complete remission of the disease in 49 % to 59 % of the population of human patients. In some modalities, the methods include achieving the complete remission of the disease in 54 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. Some modalities of this description refer to a method to achieve a primary end point in 54 % of a population of human patients who are undergoing vulgar pénfigo (PV) or pénfigo or foliaceous pénfigo (PF) includes administering the population of patients 400 mg of (R) -2- [3- [4-am ¡no-3- (2-Fluoro-4-fenox per¡dina-1carbonil] -4-meth¡l-4- [4- (oxetan-3-¡l) piperaz¡n-1-¡l] pent-2-enon (PRN1008) Twice a day (IDB) for 28 days in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where before the administration of 400 mg bid of PRN1008, the population of patients has (a) PV without treating or recurrent; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a visit for a medical checkup in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. Some modalities of this description refer to methods to achieve a rozfrnn / zznz / e / yiai final primary point in 63 % to 83 % of a population of human patients who are undergoing treatment for pénfigo that they understand: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-Am¡no-3- (2-Flore-4-fenoxi-fen¡l) p¡razolo [3,4-d] p¡rim¡din-1-¡l] p¡per¡d¡na-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-¡l) piperaz¡n-1- ¡ (PRN1008) Twice a day (IDB) for 84 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where each member of the population of human patients was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the primary final point includes the control of the disease activity (CDA) defined as a visit for a medical check -in Pénfigo In some modalities, the methods include achieving the primary end point in 68 % to 78 % of the population of human patients. In some modalities, the methods include achieving the primary end point in 73 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method to achieve a primary end point is also provided in 73 % of a rozfrnn / zznz / e / yiai population of human patients who are undergoing treatment for vulgar pénfigo (PV) or pénfigigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4 am ¡no-3- (2-Flore-4-fenox (PRN1008) Twice a day (IDB) for 84 days in combination with a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where before the administration of 400 mg bid of PRN1008, the patient population has (a) without treating or recurrent; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where the primary end point includes the control of the disease activity (CDA) defined as a visit for a medical checkup in which the formation of new PV or PF injuries ceases and the established PV and PF lesions begin to be cured. Some modalities of this description refer to methods to achieve the complete remission of the disease in 6 % to 26 % of a population of human patients who are being subject to treatment for pénfigo that they understand: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-Am¡no-3- (2-Flore-4-fenoxi-fen¡l) P¡razolo [3,4-d] pirim¡d¡n-1-¡piper¡d¡na-1-carbon¡l] -4-meth¡l-4- [4 (oxetan-3-il) pipe (PRN1008) Twice a day (IDB) for 84 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day), where each member of the human patient population was characterized by Rozfrnn / ZZNZ / E / Yiai by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the complete remission is defined as the absence of new and established lesions of Pénfigo. In some modalities, the methods include achieving the complete remission of the disease in 11 % to 21 % of the population of human patients. In some modalities, the methods include getting the disease in 15 % to 17 % of the population of human patients. In some modalities, the methods include achieving the complete remission of the complete remission of the disease in 15 % or 17 % of the population of human patients. In some modalities, the methods include achieving the complete remission of the disease in 15 % of the population of human patients. In some modalities, the methods include achieving the complete remission of the disease in 17 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method is also provided to achieve the complete remission of the disease in 15 % or 17 % of a population of human patients who are undergoing treatment for vulgar pénfigo (PV) or pénfigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenoxi-phenyl) pyrazolo [3.4-d] pyrimidin-1-il] piper¡d¡na-1-carbonil] -4-methyl4- [4- (oxetan-3-il) p¡perazin-1-il] pent-2-initrile (PRN1008) 84 days, where before the administration of 400 mg IDB of PRN1008, the patient population has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. Some modalities of this description refer to methods to obtain the complete remission of the disease in 14 % to 34 % of a population of human patients who are being subject to treatment for pénfigo that comprise: administer to each member of the population of human patients a dose of 400 mg of (R) -2 [3- [4-Am¡no-3- (2-Flore-4-phenoxi-fen¡l) Pyrazolo [3,4-d] pirim¡d¡n-1-¡l] p¡per¡d¡na-1-carbonil] -4-meth¡l-4- [4 (oxetan-3-¡¡pc) pipe times a day (IDB) for 84 days, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); and submit each member of the population of patients to a post -treatment period of 84 days after the administration of PRN1008 during which PRN1008 or corticosteroid is not administered, where each member of the population of human patients was characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points; Rozfrnn / ZZNZ / E / Yiai and A maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008, where the complete remission is defined as the absence of new and established pénfigo lesions. In some modalities, the methods include achieving the primary final point in 19 % to 29 % of the population of human patients. In some modalities, the methods include getting the primary end point in 23 % to 25 % of the population of human patients. In some modalities, the methods include getting the primary end point in 23 % or 25 % of the population of human patients. In some modalities, the methods include getting the primary end point in 23 % of the population of human patients. In some modalities, the methods include getting the primary end point in 25 % of the population of human patients. In some modalities, the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients is undergoing treatment for vulgar pénfigo or foliaceous pénfigo. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent or foliaceous pénfigo without treating or recurrent before the administration of PRN1008. In some modalities, each member of the population of human patients was characterized by vulgar pénfigo without treating or recurrent. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method is also provided to achieve the complete remission of the disease in 23 % or 25 % of a population of human patients who are undergoing treatment for vulgar pénfigo (PV) or pénfigo or foliaceous pénfigo (PF) that includes administering the population of patients 400 mg of (R) -2- [3- [4-amino-3- (2-fluoro-4-phenoxi-phenyl) pyrazolo [3,4-d] pirimidin-1-il] Day (IDB) for 84 days, and subsequently subject the population of patients to follow -up for 84 days, during this follow -up, the population of PRN1008 patients or corticosteroid is not administered; where throughout the administration of PRN1008 the population of patients is also administered to the population Rozfrnn / ZZNZ / E / Yiai of patients a corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-45 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day; where complete remission means the absence of new and established PV or PF lesions. A method to treat vulgar pénfigo (PV) or pénfigo or foliaceous pénfigo (PF) in a population of patients that understand the population a dosing regime as follows: manage (R) -2- [3- [4-amino-3- (2-fluoro-4-fenoxi-fen¡l) p¡razolo [3,4-d] p¡rim¡d¡n-1-¡l] p¡per¡d¡na-1carbon¡l] -4-meth¡l-4- [4- (oxetan-3-¡l) Pipe (PRN1008) at a starting dose of 400 mg QD (in week 1) with a stepped increase in the permitted dose in week 3 to 400 mg IDB and in week 5 to 600 mg IDB, where the dosing period ends in week 25; where the condition for the stepped increase in the dose is fine (a) The patient is not achieving control of the disease activity (CDA) or (b) is not reaching the end of the consolidation phase (ECP); where the control of the disease activity is defined as the visit in which the formation of new PV or PF injuries ceases and the established PV or PF lesions begin to be cured; where the end of the consolidation phase is defined as the visit in which new PV or PF injuries have not been developed for a minimum of 2 weeks and most of the established PV or PF lesions have been cured; where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. A method is also provided to treat a human patient who suffers from vulgar pénfigo (PV) or foliaceous pénfigo (PF) that includes: Administer to the patient a 400 mg dose of (R) -2- [3- [4-amino-3- (2-fluoro-4-fenox¡fen¡l) p¡razolo [3,4-d] p¡nm¡d¡n-1-¡l] p¡per¡d¡na-1-carbonil] -4-meth¡l-4- [4- (oxetan-3-¡l) p¡peraz¡n-1-¡ (PRN1008) Twice a day (IDB) for 168 days, where throughout the administration of PRN1008, a corticosteroid is also given to the patient at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg IDB of PRN1008, the patient has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. Some modalities of this description refer to methods to treat pénfigo in a human patient that understand: Rozfrnn / zznz / e / yiai Administer to the human patient a dose of 400 mg of (r) -2- [3- [4-amino-3- (2-Fluoro-4-phenox -Il] Pent -2enitrilo (PRN1008) twice a day, optionally in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); and assess whether the human patient is getting control of the disease activity and / or is reaching the end of the consolidation period and increasing the dose of PRN1008 up to 500 mg IDB or 600 mg bid if the human patient is not getting control of the disease activity and / or is not reaching the end of the consolidation period, where: The control of the disease activity (CDA) is defined as a visit for a medical checkup in which the formation of new pénfigo injuries ceases and the established pénfigo lesions begin to be cured; The end of the consolidation phase is defined as a medical visit in which new pénfigo injuries have not been developed for a minimum of 2 weeks and most of the established Pénfigo lesions have been cured. In some modalities, the human patient is characterized by: without treating or recurrent pénfigo; a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points; and a maintenance dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day) of a second corticosteroid, before the administration of PRN1008. In some modalities, the methods include administering PRN1008 for 13 weeks. In some modalities, the first corticosteroid administered to a member of the population of human patients and the second corticosteroid administered to the member of the population of human patients are chosen regardless of prednisone, prednisolone, and methylprednisolone. In some modalities, the first corticosteroid administered to a member of the population of human patients is the same as the second corticosteroid administered to the member of the population of human patients. In some modalities, the first corticosteroid administered to a member of the population of human patients is not the same as the second corticosteroid administered to the member of the population of human patients. A method to treat vulgar pénfigo (PV) or pénfigo or foliage pénfigo (PF) is also provided in a population of patients that includes administering a dosing regime to the population as follows: Administer (r) -2- [3- [4-amino-3- (2-fluoro-4-phenoxy-fenil) pyrazolo [3,4-d] p¡rimidin-1-il] Piperid¡na-1carbon¡l] -4-meth¡l-4- [4- (oxetan-3-¡¡¡¡ at a starting dose of 400 mg IDB (in week 1) with a stepped increase adjustment of the intrapactive dose allowed up to 500 mg IDB or 600 mg IDB, where the dosing period ends at week 13; where the condition for the stepped increase in the dose is fine (a) The patient is not rozfrnn / zznz / e / yiai achieving control of the disease activity (CDA) or (b) is not reaching the end of the consolidation phase (ECP); where the control of the disease activity is defined as the visit in which the formation of new PV or PF injuries ceases and the established PV or PF lesions begin to be cured; where the end of the consolidation phase is defined as the visit in which new PV or PF injuries have not been developed for a minimum of 2 weeks and most of the established PV or PF lesions have been cured; where throughout the administration of PRN1008 to the population of patients, a corticosteroid population is also administered to a dose of less than or equal to 0.5 mg / kg / day (<0.5 mg / kg / day); where before the administration of 400 mg QD of PRN1008, the population of patients has unrelated or recurrent PV; and (b) a cutaneous score of the Pénfigo (PDAI) disease activity of 8-60 points, and is maintained with a low corticosteroid dose therapy (LDCS) that includes administering a corticosteroid at a dose of <0.5 mg / kg / day. Pharmaceutical compositions: In some modalities of this description, PRN1008 is administered as part of a pharmaceutical composition that includes: at least one chosen compound from PRN1008 and pharmaceutically acceptable salts of it; and at least a pharmaceutically acceptable excipient. In some modalities, the pharmaceutical composition is in the form of at least one tablet. In some modalities of this description, PRN1008 is administered orally as part of a pharmaceutical composition that includes: at least one chosen compound from PRN1008 and pharmaceutically acceptable salts of it; and at least a pharmaceutically acceptable excipient. In some modalities, the pharmaceutical composition is in the form of at least one tablet. In some modalities of this description, PRN1008 is administered in the form of at least one compressed that includes: at least one chosen compound of PRN1008 and pharmaceutically acceptable salts of it; and at least a pharmaceutically acceptable excipient. In some modalities, PRN1008 is administered with a glass of water. In some modalities, PRN1008 is administered with food. In some modalities, PRN1008 is administered without food. The proportion and nature of any pharmaceutically acceptable excipient can be determined by the chosen administration route and standard pharmaceutical practice. Except in the event that any pharmaceutically acceptable conventional excipient is incompatible with PRN1008, such as that any undesirable biological effect produces or that interacts otherwise in a harmful way with any other or other components of the pharmaceutical composition, it is contemplated that its use is in the scope of this description. Some non -limiting examples of materials that can serve as pharmaceutically acceptable excipients include: (1) sugars, such as, p. eg, lactose, glucose, and sucrose; (2) Rozfrnn / ZZNZ / E / Yiai starches, such as, p. eg, corn starch and potato starch; (3) Cellulose and its derivatives, such as, p. eg, carboxymethyl cellulose of sodium, cellulose ethyl, and cellulose acetate; (4) swallow powder; (5) Malta; (6) Gelatin; (7) Talc; (8) Excipients, such as, p. eg, cocoa butter and waxes of suppository; (9) oils, such as, p. eg, peanut oil, cotton seed oil, alazor oil, 5 sesame oil, olive oil, corn oil, and soybean oil; (10) glycoles, such as, p. eg, propile glycol; (11) Polyles, such as, p. eg, glycerin, sorbitol, mannitol, and polycelen glycol; (12) Esteres, such as, p. eg, ethyl oleate and ethyl laureate; (13) Agar; (14) Buffer agents, such as, p. eg, magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) Water without pyrogens; (17) Saline dissolution Sotonica; (18) Ringer dissolution; (19) Ethyl alcohol; (20) buffered phosphate solutions; and (21) 10 other compatible non -toxic substances used in pharmaceutical formulations. Remington: The Science and Practice of Pharmacy, 21Aedition, 2005, ed. D.B. Troy, Lippinott Williams & Wilkins, Philadelphia, and Encyclopedia of Pharmaceutical Technology, eds. J. Swarbrick and J. C. Boylan, 1988-1999, Marcel Dekker, New York also describes additional non-limiting examples of pharmaceutically acceptable excipients, as well as known techniques to prepare and use them. An expert in the technique can easily select the appropriate form and route of administration depending on the disorder or condition that is going to be treated, the disorder or condition stadium, and other relevant circumstances. Rozfrnn / ZZNZ / E / Yiai Examples 20 It is intended that the following examples be illustrative and is not intended in any way that they limit the scope of the description. Abbreviations Absisis Score of the intensity of the blistering skin disorder 25 ABQOL Autoimmune quality of life of autoimmune blister diseases (assessment) AE adverse event AE quantity excreted unaltered in the urine 30 alpal phosphatase altaline Alan anine aminotransferase anava analysis analysis of variance Plasma-time concentration 35 BCR BID cell receptor twice a day (tomorrow and afternoon) BMI body mass index BP blood pressure BPM BTK CA Beats per minute Bruton Tyrosine Bruton Bruton Authority Trust Interval IC 5 CLR Renal clearance CMáx Maximum plasma concentration observed CNS CNS NETWORK SERVICES CPK Creatine Creatine Fosfoquinase CR Clinical answer 10 CRF CYP Cytochrome P450 15 dBP Blood pressure Diastolic DSG Desmogleína EC Ethics Committee (See also HREC) ECG Electrocardiogram EDC Electronic data capture 20 ELISA Immunoabsorbent Test Linked to enzyme FSH Hormone stimulating FDA Fda Fda Administration Food and Medicines GLP Good Laboratory Practices H2 H2 H2 H2 H2 H2 (receiver) HBSAG surface antigen of Hepatitis B HPMC Hipromelosa HCV HEPATITIS C Virus HDL Lipoprotein HDPE HDPE High Density polyethylene 30 HIV HIV Harmonization IMPORDICAL PRODUCT IN INVESTIGATION IMPORMATION IMPORMATION (TABLE FORMULATION) IRB Institutional Review Panel (Research Ethics Committee Rozfrnn / ZZNZ / E / Yiai 67 human) Ivig Imunoglobulin Intravenous LDL Lipoprotein Low density LPLV Last visit of the last LTFU participant LTF monitor PD Pharmacodynamic PDAI PDI Pharmacodynamics Index Pyenfigo Pyenfigo Pyenfigo PHARMACINETIC PEPFIGO PIÉFIGO PE SBP systolic blood pressure SD Standard deviation if International System of Units (International System of Units) SMC SOAT Safety Monitoring Committee Autoimmune ampoup diseases (assessment) TB tuberculosis Rozfrnn / ZZNZ / E / Yiai TEAE Emerging adverse event of treatment TGA administration of therapeutic products TMAX Maximum plasma concentration time observed TSH thyroid stimulating hormone 1½ removal of elimination WBC White blood cell WhodD Dictionary of drugs of the World Organization of the Health Xla Agammaglobulinemia linked to x Example 1: Open pilot study, phase 2, which investigates security, clinical, pharmacokinetics, and pharmacodynamics of oral treatment with the BTK PRN1008 inhibitor in patients with newly diagnosed or recurrent vulgar pénfigo The clinical study was a study of open pilot cohorts, phase 2 that investigated security, clinical, pharmacokinetics, and pharmacodynamics of oral treatment with the BTK PRN1008 inhibitor in patients with freshly diagnosed or recurrent pénfigo, such as, p. eg, vulgar pénfigo freshly diagnosed or recurrent. The study was carried out according to ethical guidelines. A key objective of drug development is to improve the risk-benefit relationship of treatment. The current care standard for the pénfigo and other diseases mediated by immunity is a high dose of CS alone or in combination with other immunosuppressive drugs, which have a high risk of AE, start of delayed action, long -term B cell depletion, and low suitability for chronic administration. CS have a long -term limited utility because the high dosages required to obtain efficiency are associated with serious adverse events. The primary objectives of the study were: (1) Evaluate the clinical security of PRN1008 in patients with pénfigo, such as, p. eg, vulgar pénfigo (PV), during a treatment period of 12 weeks (part a) or 24 weeks (part b); and (2) Evaluate the clinical activity of PRN1008 in patients with pénfigo, such as, p. eg, PV, according to the criteria of the 2014 Pénfigo S2 guideline of the European Academy of Dermatology and Venereology (EADV) (Hertl Etal., 2015), where the definition of complete remission was modified to exclude the durability part of 2 months of the definition. A secondary objective of the study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of PRN1008 in patients with pénfigo, such as, p. eg, PV. An exploratory end point of the study was to evaluate the relationship of PK and PD with each other and with efficacy and safety in this patient population. ροζίτηη / ζζηζ / ε / γίλΐ Table 1 General Dose adjustment guidelines for dose selection in the first 4 weeks in part A Clinical response BTK Valley Occupation Tolerability Action Responder400 mg IDB> 50 % well tolerated Maintain 400 mg b / gradually ddress the corticosteroids if used in combination Poorly tolerated reduce to 300 mg b / gradually ddise corticosteroids if used in combination <50 % well tolerated maintain 400 mg b / ddiscuirgradually They unleash, if not, keep the dose at 400 mg bid to tolerate the rescue criteria if they are triggered, if not, keep the dose at 400 mg bid if it is feasible <50 % well tolerated to follow the rescue criteria if they are triggered, if not, increase the dose up to 600 mg bid ID Up to 600 mg bidsi allows tolerability. Rozfrnn / ZZNZ / E / Yiai In part A (12 -week study treatment period), the initial dosage of PRN1008 was 400 mg IDB, with an intrapactive dose adjustment up to 600 mg IDB that can be allowed on the basis of the occupation of BTK and the clinical response, and corticosteroid rescue treatment, if indicated (Table 1). In Table 1, “well tolerated” is defined as the absence of Gastrointestinal grade 3 or greater, or AE non -gastrointestinal grade 2, including changes in liver function, related to PRN1008 therapy. A low corticosteroid dose could be administered (<0.5 mg / kg / day of corticosteroid, where corticosteroid was prednisone or an equivalent) in combination with PRN1008. The maximum dose of PRN1008 that can be allowed in part A, after the dose adjustment, was 600 mg bid. Patients were treated under a gradual corticosteroid decrease protocol that includes well: (1) Maintain a dose of corticosteroid for 2 weeks after the control of the disease was achieved and then reduce the dose of corticosteroid by 15 % every three weeks; or (2) Follow the gradual glucocorticoid decrease scheme described in Table 1 of Werth VP, et al., Arch Dematol. 2008 Jan; 144 (1): 25-32 (later in this memory the gradual decrease of Werth). Typically, the subjects in part A received a treatment with PRN1008 twice a day for 12 weeks, starting on day 1 and ending on the 85th day of the study, with additional 12 weeks of monitoring (the total duration of the participation of the individual subject is approximately 28 weeks). Typically, on each visit the clinical response and tolerability were valued. Table 2 General Directors for the staggered increase in dose in part B Current dose Rules for the stepped increase in the dose with inadequate clinical response 400 mg QD increase up to 400 mg IDB (allowed in the visit of week 3 or subsequently) ** 400 mg IDB increase up to 600 mg IDB (allowed in the visit of week 5 or later) ** 600 mg IDB is not possible to increase the dose. A rescue protocol with corticosteroids can be initiated. Unless tolerability problems advise the stepped increase in the Rozfrnn / ZZNZ / E / Yiai dose In part B (24 -week treatment period), the initial dosage of PRN1008 was 400 mg QD, unless the patients were eligible to move from part to part B, with a stepped increase in the intrapactive dose up to 400 mg bid allowed in or after the visit of week 3 due to insufficient clinical response (and, then, again, up to 600 mg bid. of week 5) (Table 2). The inadequate clinical response in Table 2 was determined at the discretion of the researcher. Generally, the clinical response is shown by some improvement observed in the first 2 weeks getting CDA on the visit of week 5. Typically, the subjects in part B received PRN1008 once or twice a day for 24 weeks, starting on day 1 and ending on study day 169, with a follow -up visit 4 weeks later (the total duration of the participation of the individual subject is approximately 32 weeks). A low corticosteroid dose could be administered (<0.5 mg / kg / day of corticosteroid, where corticosteroid was prednisone or an equivalent) in combination with PRN1008. Typically, on each visit the clinical response and tolerability were valued. SELECTION OF THE INITIAL DOSIFICATION OF PRN1008 400 mg bid (part a): The starting dose of 400 mg IDB was based on the dose that is known to produce ~ 70 % of BTK occupation in the valley (average occupation ~ 85 % during the day), as adjusted by the results of the relative bioavailability study, where the tablet presented ~ 70 % of the exposure of the same dose of the liquid formulation. The appropriate BTK occupations with a 400 mg IDB dosage of the IR tablet have been confirmed in many patients with pénfigo studied to date. To confirm the achievement of the target, the measurements of the BTK occupation after the first dose were rapidly processed and the doctor responsible for time for a follow -up visit on day 15 were provided (only part a). This dose level demonstrated security factors appropriate to exhibitions in chronic toxicology studies. 400 mg QD (Part B): In some, but not in all, animal studies, a dose response ratio has been observed between the occupation of BTK Predosis and clinical efficacy. As it is unknown if the dose of PRN1008 once a day will provide an adequate pharmacodynamic effect, a dose of 400 mg QD was tested in part B, with the option of increasing the dose quickly at a higher dose in or after the visit of the week 3. This dose level demonstrated security factors appropriate to exposures in chronic toxicology studies. Maximum dose of 600 mg bid: A dose level was arbitrarily chosen by 50 % higher than the higher dose level of 400 mg IDB on the previous clinical safety databases in healthy volunteers to higher exhibitions and safety factors appropriate to exposure in toxicology studies in animals. Population of the study: The study population was included by male or female patients with freshly diagnosed PVs (that is, not previously exposed to an effective induction treatment regime) or recurrent, demonstrated by biopsy, from mild to severe (PDAI 8-60), for which an initial monotherapy period of PRN1008 is clinically acceptable. As patients were allowed in the study without mucosal involvement, but with a medical history that suggested PV, some patients with clinical characteristics that suggested the foliage pénfigo variant (PF) of the disease may have been included. It was considered that patients had abandoned early study if they left the study before taking one or more dose of the study of the study. For part A, 52 patients were valued for eligibility with up to 28 days of screening. 25 patients were excluded, with 6 unable to provide written consent and agree with the valuation scheme, 6 positive in the viral screening (hepatitis B and C or HIV), 5 positive in the TB screening, 4 were not in the age range or did not have mild pv demonstrated by biopsy, and 4 were excluded for other reasons. 27 patients were included and received PRN1008 (400 mg IDB - 600 mg IDB), all starting with 400 mg IDB and three patients experiencing dose increases (one patient up to 500 mg IDB and two patients up to 600 mg IDB). 1 patient discontinued early due to an unrelated AE (acute respiratory failure) before the valuation of the primary final point CDA. 2 patients discontinued early after the valuation of the primary final point CDA, with 2 AE not related (pancreatic pseudoquist; chest pain) reported between the valuation of the primary final point CDA and the compliance with the treatment. 24 included patients underwent a prostrate assessment of 12 weeks. For part B, 18 patients were valued for eligibility with up to 28 days of screening. 15 patients were included and received 400 mg QD allowing the adjustment of staggering increase in intrapactive dose (400 mg IDB, 600 mg IDB). 1 patient discontinued in week 9 due to a worsening of the pénfigo that began during the screening after stopping the MMF, which continued, giving rise to hospitalization in week 9. Demographic characteristics in the baseline for patients included in parts A and B are summarized in Table 3. In Table 3, Moderate-Grave included patients with serious, recurrent disease, according to PDAI gravity quartiles for recurrent disease in front of slight-moderate in newly diagnosed disease. Rozfrnn / ZZNZ / E / Yiai Table 3 demographic characteristics CHARACTERISTICS PART A (N = 27) PART B (N = 27) MIDDLE AGE, YEAR (SD, RANGE) 52 (9, 37-72) 46 (9.5, 30-64) SEX, N (%) MALE 12 (44) 8 (53) FEMALE 15 (56) 7 (47) Type of Pénfigo, N (%) Pénfigo vulgar 23 (85) 13 (88) (11) 1 (7) None 1 (4) 1 (7) Average time from the diagnosis of Pénfigo, years (mean, range) 6 (7, 0-25) 1.14 (1.35, 0-5.3) Average PDAI score, points (SD, range) 19 (11.8-43) 15.5 (7.5, 8-36) Severity of the disease, n (%) Pdai (Mild-moderate) 11 (41) 8 (53) Pdai> 15 (Moderate-Grave) 16 (59) 7 (47) Average dose of CS at the entrance, mg / day (sd, range) 14 (11.0-30) 21 (14, 0-50) Pozfrnn / ZZNZ / E / Yiai Inclusion criteria (part A and part B unless indicated below): The following inclusion criteria were used to inform about the inclusion of patients in this study. 1. Male or female patients, aged 18 to 80 years of age, with lighting PV demonstrated by biopsy (positive positive immunofluorescence and appearance in Microscopy H and E), in part A (Pdai 8 to 45) and slight PV in Part B (Pdai 8 to 60) 2. Patients recently diagnosed or recurrent for whom an initial monotherapy period of PRN1008 or combination therapy with a low dose of corticosteroids (<0.5 mg / kg of prednis [OL] ona or equivalent) is clinically acceptable), provided that a gradual decrease in the treatment regime with corticosteroid with a good clinical response is anticipated with a good clinical response to PRN1008 3. BMI> 17.5 and <40 kg / m2 (part A single) 4. Hematological, hepatic, and adequate renal (Absolute neutrophil count> 1.5 x 109 / l, Hgb> 9 g / dl, platelet count> 100 x 109 / l, ast / alt <1.5 x uln, albumin> 3 g / dl, creatinine <uln Creatinine <1.5 x uln (part b) 5. Female patients who have reproductive potential must agree, during the duration of active treatment in the study, in using an effective means of contraception (hormonal contraception methods that inhibit ovulation, intrauterine device, intrauterine hormonal release system, bilateral tubañca ligation, companion subject to vasectomy, condoms or sexual abstinence). Unless they are surgically sterile, postmenopausal women must have menopause confirmed by FSH test. 6. Able to provide written informed consent and agree with the valuation scheme. Exclusion criteria: The following exclusion criteria were used to inform about the inclusion of patients in this study. 1. Prior use of a BTK inhibitor The patients included in a previous version of the protocol that were still with their active treatment period of 12 weeks with PRN1008 were eligible to continue the treatment, initially with their current dose level, under the modified protocol for additional 12 weeks, that is, 24 weeks in total, after the review and signing of the consent of the patient approved by the EC. Patients who completed part A and did not discontinue the study due to a medical condition that could compromise safety assessments or by an adverse event related to PRN1008 can be screening for their entrance under part B. 2. Pregnant women or infants 3. QTC ECG discoveries> 450 mseg (men) or> 470 mseg (women), poorly controlled atrial fibrillation (that is, symptomatic patients or a ventricular ventricular rate of more than 100 beats / min in ECG), or other clinically significant anomalies 4. A history of malignancy of any kind, different from leather cancers other than surgically removed melanoma or cervical cancer in situ in the 5 years before the day of dosing 5. Use of immune response modifiers with the following periods before day 1: as concomitant therapy, other immune response modifiers not detailed in this exclusion apart from corticosteroids; 1 week ', cyclophosphamide; 4 weeks'. MG, Kinret (Anakinra) and Enbell (ETERECPT); 12 weeks ·. Remicade (Inflyximab), Humira (Adalimumab), Simponi (Golimumab), ORENCIA (Aplercept), ACTEMRA (Tocilizumab), Cimzia (Certolizumab), Cosentyx (Secukinumab), Plasmapheresis; 6 months'. Rituxan / Mabthera (rituximab), ofatumumab, any other anti-cd20 antibody, other biological durable products 6. More than 0.5 mg / kg of Prednis (OL) ona per day (“low dose of corticosteroids”) in the two weeks prior to day 1 7. Use of protons pump inhibitors such as omeprazole and esomeprazole (it is acceptable 8. Concomitant use of inductors or known inhibitors from strong to moderates from CYP3A (Appendix 2) in the 3 days or 5 semi -trades (which is longer) of the dosage of the drug drug 9. Use of drugs that are substrates sensitive to cyp3a (Appendix 3) with a narrow therapeutic index in the 3 days or 5 semi -experience (which is longer) of the dosage of the Rozfrnn / Zznz / E / Yiai study drug including, but not limited to, alfentanil dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or terfenadine 10. Any drug in research has received (or is currently using a research device) in the 30 days before receiving the first dose of study medication, or at least 5 times the respective elimination semi -removidated time (whatever is longer) 11. History of drug abuse in the previous 12 months 12. Alcoholism or excessive use of alcohol, defined as regular consumption of more than approximately 3 standard drinks per day 13. Nausea and refractory vomiting, bad absorption, external biliary derivation, or significant intestinal resection that would avoid adequate absorption of the drug drug 14. Anorexia nervosa history or periods of three months or more low body weight (BMI <17.5) in the last 5 years 15. Donation of a unit or more of blood or blood products in the 4 weeks before day 1 16. solid organ transplant history 17. Epilepsy history or other forms of seizure in the last 5 years 18. Positive in HIV screening, hepatitis B (surface antibodies and centrals not related to vaccination), or hepatitis C (anti-HCV antibody confirmed with HEP C RNA c) 19. Positive in interferon-gamma liberation test (IGRA) (eg, T-Spot TB, Quantiferon®-TB Gold, or Quantiferon®-TB Gold Plus (QFT Plus) in the screening. Unless the Patient TB Latent and the following 3 conditions are all true: to. Thorax X -rays do not show evidence to suggest active tuberculosis disease (TB) b. There are no clinical signs and symptoms of pulmonary and / or extra-pulmonary disease c. Documented reception of one of the following prophylactic treatment regimes: i. Oral Daily Isoniazid for 6 months or II. Daily oral rifampina (rif) for 4 months or III. Isoniazid and Rifapentina weekly for 3 months (3HP) In a case -by -case basis, after the discussion and approval by the sponsor, a local TB trial that is negative can be used for eligible and is considered equivalent to 1 of the previous trials. For example, if a quantiferon®-TB Gold, or quantiferon-tb Gold Plus (qft plus) is positive and a local blood test or t-spot tb test is negative, the patient can be included using the local result after the approval of the sponsor. 20. History of serious infections that require intravenous therapy with the recurrence potential 21. LIVE vaccine in the 28 days prior to the baseline or plan to receive one during the Rozfrnn / ZZNZ / E / Yiai study 22. Any other disease, condition, or clinically significant medical history that, in the researcher's opinion, would interfere with the security of the subject, study evaluations, and / or study procedures Previous therapy: The use of immune response modifiers in the following periods before day 1: (1) one week for cyclophosphamide was not allowed; (2) four weeks for Kinret® (Anakinra), Intravenous Globulina Gamma (MG), and Enbell® (ETERECPT); (3) 12 weeks for Recycade® (Inflyximab), Humira® (Adalimumab), Simponi® (Golimumab), Orencia® (Alecept), Acttemra® (Tocilizumab), Cimzia® (Certolizumab), Cosentyx ™ (Secukinumab), plasmapheresis; and (4) 6 months for Rituxan® / Mabthera® (rituximab), ofatumumab, any other anti-cd20 antibody, or any biological product of lasting action. Concomitant therapy: The concomitant use of immunosuppressive medication, different from low corticosteroid doses, was avoided, unless rescue criteria were triggered. The concomitant use of inductors or known inhibitors from strong to moderate CYP3A was avoided in the 14 days or 5 semi -trades (which is longer) dosage with PRN1008. The use of cyp3a sensitive drugs was avoided with a narrow therapeutic index in the 14 days or 5 semi -trades (which is longer) dosage with PRN1008 including, but not limited to, alfentanil Sirolimus, tacrolimus, or terfenadine. Protons pump inhibitors were not allowed. The use of Prednis (OL) Oral Oral was considered permissible in some circumstances. For admission in the study, the dose of prednis (OL) oral ONA in the 2 weeks before day 1 could be not greater than 0.5 mg / kg per day (inhaled and mucosal corticosteroids are allowed [for the symptomatic treatment of oral lesions]). When patients entered the study with low dose of corticosteroids, the regime could be maintained during the initial 2 weeks of PRN1008 therapy. In the revision of the 15th, a good clinical response to PRN1008 could allow the gradual decrease of corticosteroid to start using Werth's gradual decrease. In some circumstances, corticosteroids could be added or the dose increased, with or without the cessation of PRN1008, as clinically appropriate. Valuations: After providing written informed consent, the subjects typically completed the screening assessments in the 28 days prior to the first dose of PRN1008: (1) Review of the medical history and concomitant medication; (2) Valuations of PDAI, Absis; (3) Review of the inclusion and exclusion criteria; (4) Measurement of height and weight; (5) physical exam; (6) ECG of 12 derivations; (7) vital signs (blood pressure, heart rate, breathing rate, and temperature); (8) Clinical laboratory test (hematology, coagulation, serum chemistry, and urine analysis), HIV, hepatitis B (surface antigen and central antigen and antibodies), hepatitis C (anti-HCV antibody confirmed with HEP C RNA); (9) TB screen screening with the T-Spot TB, Quantiferon®-TB Rozfrnn / ZZNZ / E / Yiai Gold, or Quantiferon®-TB Gold Plus (QFT Plus); (10) serum pregnancy essay for women with potential to have children; (11) FSH (in postmenopausal women who are not surgically sterile alone); (12) Skin biopsy if no longer has been performed: Injury for staining with H and E, perilesional for direct immunofluorescence. Pdai and Absis assessments were used to monitor the activity of Pénfigo's disease. For most of the subjects in parts A and B, abbreviated physical exams, Pdai, and absis assessments were performed in the following assessments: (1) day 1, week 1 (predoses); (2) day 15, week 3 (+ 3 days); (3) day 29, week 5 (+ 3 days); (4) day 57, week 9 (+ 7 days); (5) day 85, week 13 (± 7 days); (6) day 113, week 17 (± 7 days); (7) day 141, week 21 (± 7 days); (8) day 169, week 25 (± 7 days); (9) Day 197, Week 29 (± 7 days); and (10) any unchanging visit. Photography was used to document changes in skin disease, when appropriate. ABQOL and TABQOL assessments were used to monitor the quality of life of the subjects. For most of the subjects in parties A and B, the valuations of ABQOL and Tabqol were made in the following valuations: (1) day 1, week 1 (predoses); (2) day 15, week 3 (± 3 days); (3) day 29, week 5 (± 3 days); (4) day 57, week 9 (± 7 days); (5) day 85, week 13 (± 7 days); (6) day 113, week 17 (± 7 days); (7) day 141, week 21 (± 7 days); (8) day 169, week 25 (± 7 days); (9) Day 197, Week 29 (± 7 days); and (10) any unchanging visit. The specific assessments to evaluate the security of the treatment included the following: 1) the frequency and type of the AE; (2) Clinical Laboratory trial; (3) SNAQ appetite questionnaire; and (4) vital signs. Typically, patients remained under observation in the clinic for 2 hours after the administration of the first dose of PRN1008 and until the PK sample was taken. Primary results measures: Primary security results measures were incidence of AE emerging treatment (TEAE), including clinically significant changes in physical examination, laboratory tests, and vital signs. Primary efficacy results measures were the proportion of subjects who were able to obtain control of the disease activity (CDA) in the 4 weeks from the beginning of the PRN1008 treatment without the need for the dose of prednis (OL) ONA> 0.5 mg / kg. Secondary results measures: The following final points of the clinical activity were also valued: (1) Proportion of subjects capable of getting CDA without corticosteroids in 4 weeks; (2) Proportion of subjects capable of getting a complete response (CR) without corticosteroids in 12 weeks (and 24 weeks in part B); (3) Proportion of subjects capable of getting CR without the need for dose of prednis (OL) over 0.5mg / kg in 12 weeks (and 24 weeks in part B); (4) time until CDA; (5) time to CR; (6) time until the end of the consolidation phase; (7) Time until recurrence after discontinuation of treatment with PRN1008; (8) cumulative use of corticosteroid during the first 12 weeks (and 24 weeks in part b); (9) Change from the baseline in the scores of the Pénfigo disease area (PDAI) and score of the autoimmune rozfrnn / zznz / E / Yiai (ABSIS) blistering cutaneous disorder in each monitoring visit; (10) Change from the baseline in the scores of the quality of life of autoimmune blister diseases (ABQOL) and quality of life with treatment of autoimmune blister diseases (Tabqol) on each follow -up visit; and (11) change from the baseline in appetite (SNAQ score) on each tracking visit. The final points of the clinical activity were as defined by the 2014 Pénfigo S2 guideline (Hertl et al. 2015) with the exception that CR was defined as CR in a single point of time instead of being present for> 2 months. PK / PD measures: The measures of the PK investigated results included plasma concentrations of PRN1008 approximately at the time of maximum concentration on day 1 and at different times later during the ambulatory dosage. The measures of the investigated PD results included the BTK occupation percentage for individuals in peripheral blood mononuclear cells (PBMC) at 2 and 24 hours after the first dose of PRN1008 and at varied subsequent times during the ambulatory dosage, as well as the change from the baseline in the levels of self-anticipation ant The exploratory analysis of PK / PD examined the effects, if there were, covariables in PK and / or PD, and the relationship between PK, PD, and effectiveness in this population. Analysis populations: Four study populations were defined: screening population; Security population; Effective population; and population of pharmacokinetics. All participants who provided informed consent were included in the screening population and have screening assessments evaluated for participation in the study. All participants who had received at least one dose of PRN1008 (security population) were included in the security analysis. The security analysis population was defined for all security analyzes. All patients who received at least one dose of PRN1008 (population of efficiency) were included in the efficacy analysis. The response of the subjects and the progression of the disease were determined using the PDAI, Absis, Abqol, and Tabqol scores. The pharmacokinetic population included participants who provided adequate plasma concentration data to allow PK analysis. Participants could be excluded from the population of PK if they significantly violated the criteria of inclusion or exclusion, they were significantly diverted from the protocol, or if the data were not available or were incomplete, all of which can influence the analysis. Clinical adverse events: An adverse event (AE) is any unwanted medical appearance in a participant or participant in a clinical investigation to which a pharmaceutical product is administered and that does not necessarily have a causal relationship with the intervention. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory discovery, for example), symptom, or Rozfrnn / ZZNZ / E / Yiai disease temporarily associated with the use of a research product, it is already considered or not related to the product. The researchers were instructed to inform in detail of all the AEs found during the clinical study in the source documents, from the date of the consent of the patients to the follow -up visit. The researchers were also instructed to inform that the pre -existing conditions that worsen during a study were instructed as AE, with the exception of the disease under study since there could be a variation in the activity of the Pénfigo disease that is intended to be captured in other measurements. The researchers were instructed to classify the AE on the basis of NCI CTCAE, version 4.0 or higher. For any AE not found in the CTCAE, the following intensity classification could be used: Grade 1: Mild; asymptomatic or minor symptoms; only clinical or diagnostic observations; intervention not indicated. Grade 2: Moderate; Minimum, local or non -invasive intervention indicated; Limit the appropriate instrumental activities for the age of daily life. Grade 3: serious or medically significant, but it is not potentially deadly; hospitalization or extension of the indicated hospitalization; disability; Limit self -life self -life activities. Grade 4: potentially mortal consequences; Urgent intervention indicated. Grade 5: Death related to AE. The researchers were instructed to use their knowledge of the participant in the study, the circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an AE is considered or not related to the drug drug, indicating “yes” or “no” according to this. The researchers were urged to consider the following guideline to determine if an AE was related to the study of the study: (1) Temporary relationship of the start of the event with the beginning of the drug drug; (2) Course of the event, especially considering the effects of dose reduction, discontinuation of the study of the study, or reintroduction of the drug drug (if applicable); (3) known association of the event with the drug drug or with similar treatments; (4) known association of the event with the disease under study; (5) presence of risk factors in the participant in the study or use of concomitant medications that are known to increase the appearance of the event; and (6) presence of factors not related to the treatment that is known that they are associated with the appearance of the event. A severe adverse event (SAE) is any experience (clinical AE or abnormal laboratory trial) that suggests a significant danger, contraindication, side effect, or caution. A SAE must fulfill at least one of the following criteria at any dose level: (1) is fatal (it gives rise to death); (2) It is potentially deadly; (3) It requires hospital admission or prolongation of existing hospitalization; (4) results in persistent or significant disability / disability; (5) is an anomaly / congenital birth defect; or (6) is medically significant or requires intervention to prevent one or another of the results listed above. Rozfrnn / ZZNZ / E / Yiai Study design, part A: Part A was a phase 2 multi -center, open, one -arm Patients from 13 sites in Australia, Croatia, France, Greece, and Israel signed up for inclusion. 52 patients were screening in Australia, Croatia, France, Greece, and Israel, with 25 who did not meet the eligibility criteria. The high rate of failure in the screening was due to patients with a positive trial for hepatitis B or C (n = 6) or tuberculosis (n = 5). 27 patients were included and included in security analysis. A total of 26 patients were included in the modified ITT population (MITT) used for primary efficacy analysis, with a patient excluded due to an AE not related to treatment. Two other patients abandoned the study due to AE not related to treatment, leaving a total of 24 patients who completed the study. The average age of the patients was 52.1 (Rank: 37-72), and most patients were white (81.5 %) and women (55.6 %). Nine patients (33.3 %) had a recent diagnosis and 18 (66.7 %) were recurrent. The average time from the diagnosis to the screening was 6 years (range: 0-25). Eleven patients had mild to moderate pénfigo, and 16 patients had moderate to serious pénfigo. Twenty -six patients received CS medication at some point during the study. A total of 22 patients were from the PV phenotype (13 anti-DSG 3+, 10 anti-DSG 1 / 3+), three were from the PF phenotype (anti-DSG 1+), and a patient was double negative for anti-DSG 1 / 3. The median dose of CS at the entrance to the study was 14 mg / day, varying 0-30 mg / day. Patients received an initial dose of 400 mg of PRN1008 twice a day (IDB) with possible dose adjustment up to 600 mg IDB at the discretion of the researcher. The duration of treatment was 12 weeks with additional 12 weeks of monitoring without treatment. The dose to three patients was staggered due to a worsening of the disease activity. A patient who had obtained CDA on the 15th increased up to 500 mg IDB with CS on day 34. Two additional patients were increased up to 600 mg bid; The first on the 23rd with a dose of CS of 25 mg (they got CDA on day 29) and the second on day 57. Patients were allowed to receive no more than 0.5 mg / kg / day of CS in addition to the regime with the drug drug, unless necessary for the "rescue" of the disease. Patients were monitored throughout the study and valued for vital signs, adverse events (AE), concomitant medication, PK / PD, and other clinical laboratory trials. The final point of primary efficacy was the proportion of patients who managed to control the disease activity (CDA) in four weeks from the beginning of the treatment with PRN1008 with a dose of CS of <0.5 mg / kg / day (Murrell DF et al., 2008). The CDA was defined as the time in which the formation of new injuries ceased and the established injuries began to be cured. The final primary security point was the incidence of emerging adverse events of treatment (TEAE), including clinically significant changes in physical examination, laboratory tests, and vital signs. The secondary end points included PK / PD data as measured by the occupation of BTK in peripheral blood mononuclear cells (PBMC) at two and 24 hours after the first dose of PRN1008 Rozfrnn / ZZNZ / E / Yiai and the change from the baseline in the levels of anti-DSG 1 and anti-DSG 3 to different time. Due to the small sizes of the samples, all the values ​​P derived from inferential analyzes were considered informative. In general, all significant trials were bilateral at a significance level of 0.05. All tests were done without adjustment for multiplicity or multiple comparisons. Bilateral IC of 80 % and 95 % of the response rate for the final points of effectiveness were provided. All patients, except one, had the therapeutic levels of BTK occupation in peripheral white cells (Diana> 70 %). A high occupation was achieved on day 1 after the first dose, confirming that an adequate initial dose was used. The median BTK's occupation on day 1 in two hours posdoses was 88 %, with an average predoses in the stationary state of 87 %. The rapid systemic clearance and slow unlock kinetics gave rise to minimum plasma levels of 9.5 ng / ml at 12 hours posdoses (Valle point) with a high occupation of BTK maintained of 87 %. of 26 (54 %) patients got CDA with a low dose of CS about day 29 (after a period of 4 weeks) (Fig. 1). This end point in the dosing subgroups of 400, 500, and 600 mg IDB was 12 of 23 (52 %), 1 of 1 (100 %), and 1 of 2 (50 %), respectively. A total of three patients got CDA in O Before the visit of week 5 without the use of CS (Fig. 2). 19 of 26 (73 %) patients got CDA with a low dose of CS about 85 (Fig. 1, 2). of 26 (23 %) patients got CR during the study period (Fig. 3). Four patients (15 %) got CR with dose of Cs <0.5 mg / kg / day on the 85 <0.5 mg / kg / day in the monitoring period (about 141). The average dose of CS was 14 mg / day (SD = 11) in the baseline and 12 mg / day (SD = 10) after 12 weeks of treatment for all patients. For patients who achieved CR, the average dose of CS was 8 mg (range: 1-20 mg) at the time they got CR. The median CR duration was 96 days post -treatment, during which the average dose of CS was 8 mg / day (range: 0.720 mg / day). A median 70 % reduction was observed in PDAI scores and an associated reduction in anti-DSG 3 antibodies for 12 weeks of treatment (Fig. 4, 5). Reductions in PDAI scores were observed as soon as two weeks with therapy in patients with moderately serious disease. In 11 patients with milder disease, PDAI scores decreased in the first four weeks of therapy and all patients had 5 or less PDAI scores on the visit of the 85th. A median reduction of self -antibodies levels of up to 65 %, including in patients who had high levels of autoantibody in the baseline, was observed. The results were similar in all subgroups, including new cases against chronicles, Rozfrnn / ZZNZ / E / Yiai Anti-DSG antibodies degrees 1 and 3 <100 against> 100, and groups of patients with mild pénfigo compared to moderate to serious. CDA rates in recurrent and newly diagnosed patients were 13 of 18 (72 %) and 6 of 8 (75 %), respectively. In patients with an anti-DSG 3 antibody, CDAs were slightly higher (64 %) than in those of the MITT Global population. Globally, PRN1008 quickly improved clinical symptoms with> 50 % of patients in part A CDA in four weeks and a median global reduction in the PDAI score of 70 %. The efficacy throughout the subgroups varied from 43-64 %, which suggests that the success of the treatment is not influenced by the characteristics of the disease and can be effective for all patients diagnosed with pénfigo. 90 % of patients did not require a staggered increase in the dose to get a response. The high proportion of patients who achieved CDA on week 4 (54 %), despite the lack of reduction in anti-DSG 3, suggests that this may be the result of a rapid and independent anti-inflammatory effect of the reduction of autoantibodies. On week 12, the reduction was observed both in the PDAI score and the anti-DSG 3 levels. This observation can be attributed to the three simultaneous action mechanisms of PRN1008, that is, rapid anti-inflammatory effects, neutralization of pathogenic autoantibodies, and blocking the production of autoantibodies. Notably, 2 / 3 of the study population in part A were patients with recurrent pénfigo who had lived with this condition during a significant amount of time (average: 6 years) and have probably been refractory to multiple treatments. Additionally, more than 50 % of the patients included had PDAI scores consisting of moderate to serious pénfigo. Most of the other treatments of Pénfigo have only been studied in newly diagnosed patients or those who have been treated for up to 2 years (Chams-Davatchi C et al., 2013). In this study, PRN1008 demonstrated effectiveness in a population that is very difficult to treat and more representative of the demographic characteristics of this affection in the real world. PRN1008 also shows potential to reduce the use of CS compared to the current care standard. The patients achieved an improvement of symptoms with CS under none (average fall from 14 mg / day in the baseline at 8 mg / day in Cr), which is favorably compared with the standard standard of usual care for the Pénfigigo (typically 1 mg / kg / day or at least 60 mg / day) (Gregoriou s ETA al., 2015; Cholera M et al., 2016). Three patients got CDA in O before week 5 without the use of CS and four additional patients got CR in week 13 without the use of CS. Only three patients needed a staggered dose increase beyond the 400 mg IDB standard, and only 4 patients needed rescue with CS> 0.5 mg / kg in 12 weeks without PRN1008. It is possible that a longer duration of PRN1008 therapy may allow an additional reduction of or even the discontinuation of the use of Cs. If it were true, this would reduce the risk of CS -induced AE that are common with current therapies and mitigate the adverse consequences of long -term high -intensity CS therapy (Hwang JL et al., 2014; Rostaing L et al., 2016) of 27 patients (74 %) in the security population experienced a TEAE. The TEAE reported> 10 %of the patients are shown in Appendix 17. The AEs that were valued as Rozfrnn / ZZNZ / E / Yiai related to the drug drug included náusea (15 %), upper abdominal pain (11 %) and headache (11 %). Most AE had a mild to moderate gravity (94 / 97 were from grade 1 or 2) and were frequently transitory. Three patients experienced AE Serious (SAE). The first and only SAE related to treatment was cellulite (grade 3) on the 26th in a patient with type II diabetes with recurrent pénfigo for nine years. After a three -day course of IV antibiotics during which the drug drug was suspended, the patient was discharged and completed the 12 weeks of treatment. The second SAE was Pseudoquiste Pancreatic discovered on day 29, after which the patient abandoned the study for elective surgery. The third SAE was acute respiratory failure (day 8) due to inflammation of a non -diagnosed congenital pulmonary kidnapping. The patient did not recover and died 34 days after the last exposure to PRN1008; It was judged that the cause of death was cerebral hernia-Embolism of the cerebral artery after pulmonary surgery. The security results for PRN1008 in part A indicate a favorable risk / benefit profile. Most Teae reported in this study were mild and transitory, and there were no cases of AE commonly associated with the BTKI marketed, such as major hemorrhage, atrial fibrillation, or thrombocytopenia / neutropenia. The limitations of the study for part A include those typically associated with an open test design, such as the absence of a control group. Therefore, the data should be interpreted carefully, and a placebo controlled test is necessary to provide a more robust evaluation. The duration of the study was short, with 12 weeks of treatment and 12 weeks of monitoring, and more long -term data is necessary. The sample size of 27 patients was small. However, Pénfigo is a relatively rare disease, and, therefore, any study in this disease area would have a relatively modest size. Although approximately half of the study population was included from Greece, the clinical and demographic characteristics of patients in the ITT population can be widely representative of patients with pénfigo. Study design, part B: Part B was a phase 2 multi -center, open, one -arm Patients received an initial dose of 400 mg of PRN1008 once a day (QD) with possible dose adjustment up to 600 mg IDB at the discretion of the researcher. The treatment duration was 24 weeks with additional 4 weeks of monitoring without treatment. A patient abandoned due to the worsening of the pénfigo in week 5. In part B, treatment with PRN1008 provided high CDA rates (Fig. 6, 7, 8a, 8b). Patients with a dosing of 400 mg QD were able to get CDA at 4 weeks with a low dose of corticosteroid, but at lower rates compared to the IDB dosage. The overall CDA rate at 12 weeks was 80 % (12 of 15 patients). Patients with a dosing of 400 mg QD had lower full remission rates at 12 weeks (Fig. 9a, 9b) compared to IDB dosage. However, around 24 weeks, Rozfrnn / ZZNZ / E / Yiai a 94 % reduction in the median PDAI activity score and a 79 % reduction in the average score of PDAI activity were observed for patients included in part B (Fig. 10, 11). The median Pdai was from 12 on day 1 to 4 at 12 weeks and 1 to 24 weeks, with 10 of 15 patients (67 %) having reached a PDAI from 1 or 0 to 24 weeks. In addition, 24 weeks of treatment with PRN1008 decreased the daily use of corticosteroids (Fig. 10). Although the cumulative dose of steroids increased between the first 12 weeks and the second 12 weeks in part A, the opposite was true in part B. Globally, PRN1008 was well tolerated in part B and continued supporting a positive benefit / risk for patients with pénfigo. All AE related to treatment were slight and transient. The adverse events related to the treatment in part B were consistent with those observed in part A, having the most common AE a gastrointestinal origin. In part B, 2 of 15 patients reported a mild related infection (1 event each: grade nasopharyngitis 1; Grade 1 tracheitis). The AE related to the treatment with an incidence greater than 10 % were nausea, abdominal distension, infection, and oropharyngeal pain that were mild to moderate (grade 1 and 2). Certain documents refer to this application in short appointment format. Next, the most detailed appointments for referenced documents are provided. Byrd JC, Furman rr, Coutre Se, Flinn Iw, Burger Ja, Blum Ka, Grant B, Shaman JP, Coleman M, Wierd Targeting BTK with ibrutinib in relapsed chronic lymphoclytic leukemia. N English J Med., 369 (1): 32-42, 2013. Bizikova P, Olivry T, Mamo LB, Dunston SM. SERUM AUTOANTIBODY PROFILES OF IGA, IGE AND IGM IN CANINE PEMPHIGUS FOLIACEUS. Vet Dermatol 2014; 25: 471-E75. 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The claims or descriptions that include “o” or “y / o” between at least one member of a group are considered satisfied if one, more than one, or all the members of the group are present in, are used in, or are otherwise relevant for a product or process given unless it is indicated otherwise or otherwise evident from the context. The description includes modalities in which exactly a member of the group is present in, is used in, or is otherwise relevant for a given product or process. The description includes modalities in which more than one, or all group members are present in, are used in, or otherwise relevant for a given product or process. When ranges are provided, the final points are included. In addition, unless otherwise indicated, or otherwise, from the context and understanding of an expert in the technique, the values ​​that are expressed as ranges can assume any specific value or sub -ranger within the ranges indicated in different modalities of the description, to the tenth of the Rozfrnn / ZZNZ / E / Yiai unit of the lower limit of the range, unless the context clearly dictates otherwise. The above description has been described in some detail as an illustration and example, for the purposes of clarity and understanding. Therefore, it should be understood that the above description is intended to be illustrative and not restrictive. The scope of the description should be determined, therefore, not with reference to the previous description, but in its place it should be determined with reference to the following attached claims, together with the complete scope of those equivalent to those who are entitled to these claims.

Claims

1. A method of treating pemphigus in a human patient in need thereof comprising administering to the human patient a dose of at least 400 mg of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxyphen¡l)p¡razolo[3,4-d]p¡r¡m¡n-1-¡l]p¡peradina-1-carbonyl]-4-methyl-4-[4-(oxetan-3-¡l)p¡peraz¡n-1-¡l]pent-2enenitrile (PRN1008) once daily (QD) for at least 14 days.

2. The method according to claim 1, comprising administering to the human patient a dose of at least 400 mg of PRN1008 QD for 14 to 168 days.

3. The method according to claim 1 or 2, comprising administering to the human patient a dose of at least 400 mg of PRN1008 QD for 14 days.

4. The method according to claim 1 or 2, comprising administering to the human patient a dose of at least 400 mg of PRN1008 QD for 28 days.

5. The method according to claim 1 or 2, comprising administering to the human patient a dose of at least 400 mg of PRN1008 QD for 84 days.

6. The method according to claim 1 or 2, comprising administering to the human patient a dose of at least 400 mg of PRN1008 QD for 168 days.

7. The method according to claim 1, comprising administering to the human patient a dose of 400 mg of PRN1008 QD for at least 14 days.

8. The method according to claim 1 or 7, comprising administering to the human patient a dose of 400 mg of PRN1008 QD for 14 to 168 days.

9. The method according to any of claims 1, 7, or 8, comprising administering to the human patient a dose of 400 mg of PRN1008 QD for 14 days.

10. The method according to any of claims 1, 7, or 8, comprising administering to the human patient a dose of 400 mg of PRN1008 QD for 28 days.

11. The method according to any of claims 1, 7, or 8, comprising administering to the human patient a dose of 400 mg of PRN1008 QD for 84 days.

12. The method according to any of claims 1, 7, or 8, comprising administering to the human patient a dose of 400 mg of PRN1008 QD for 168 days.

13. The method according to claim 1, comprising: administering to the human patient a first dose of 400 mg of PRN1008 QD for 14 days; and administering to the human patient a second dose of 400 mg of PRN1008 twice a day (BID) for at least 14 days after the administration of the first dose.

14. The method according to claim 13, comprising administering to the human patient a second dose of 400 mg of PRN1008 BID for 14 to 154 days after administration of the first dose.

15. The method according to claim 1, comprising: administering to the human patient a first dose of 400 mg of PRN1008 QD for 14 days; and administering to the human patient a second dose of 400 mg of PRN1008 twice a day (BID) for 14 days after the administration of the first dose; and administering to the human patient a third dose of 600 mg of PRN1008 BID after the administration of the second dose.

16. The method according to claim 15, comprising administering to the human patient a third dose of 600 mg of PRN1008 BID for a maximum of 140 days after the administration of the second dose.

17. The method according to claim 15, comprising administering to the human patient a third dose of 600 mg of PRN1008 BID for 56 days after the administration of the second dose.

18. A method for treating pemphigus in a human patient in need comprising administering to the human patient a dose of at least 400 mg of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxypheni1)prazolo[3,4-d]primidin-1-11]piperidine-1-carboni1]-4-methyl-4-[4-(oxetan-3-11)piperazin-1-11]pent-2-enenitrile (PRN1008) twice daily (BID) for at least 14 days.

19. The method according to claim 18, comprising administering to the human patient a dose of at least 400 mg of PRN1008 BID for 14 to 84 days.

20. The method according to claim 18 or 19, comprising administering to the human patient a dose of at least 400 mg of PRN1008 BID for 14 days.

21. The method according to claim 18 or 19, comprising administering to the human patient a dose of at least 400 mg of PRN1008 BID for 28 days.

22. The method according to claim 18 or 19, comprising administering to the human patient a dose of at least 400 mg of PRN1008 BID for 84 days.

23. The method according to claim 18, comprising administering to the human patient a dose of 400 mg of PRN1008 BID for at least 14 days.

24. The method according to claim 18 or 23, comprising administering to the human patient a dose of 400 mg of PRN1008 BID for 14 to 84 days.

25. The method according to any of claims 18, 23, or 24, comprising administering to the human patient a dose of 400 mg of PRN1008 BID for 14 days.

26. The method according to any of claims 18, 23, or 24, comprising administering to the human patient a dose of 400 mg of PRN1008 BID for 28 days.

27. The method according to any of claims 18, 23, or 24, comprising administering to the human patient a dose of 400 mg of PRN1008 BID for 84 days.

28. The method according to claim 18, comprising: administering to the human patient a first dose of 400 mg of PRN1008 BID for at least 14 days; and administering to the human patient a second dose of 500 mg of PRN1008 BID after the administration of the first dose.

29. The method according to claim 28, comprising administering to the human patient a first dose of 400 mg of PRN1008 twice daily for 14 to 28 days. rozfrnn / zznz / E / YiAi 30. The method according to claim 28, comprising administering to the human patient a first dose of 400 mg of PRN1008 BID for more than 28 days.

31. The method according to claim 28, comprising administering to the human patient a first dose of 400 mg of PRN1008 BID for 33 days.

32. The method according to any of claims 28 to 31, wherein PRN1008 is administered to the human patient for a maximum of 84 days.

33. The method according to claim 18, comprising: administering to the human patient a first dose of 400 mg of PRN1008 BID for at least 14 days; and administering to the human patient a second dose of 600 mg of PRN1008 BID after the administration of the first dose.

34. The method according to claim 33, comprising administering to the human patient a first dose of 400 mg of PRN1008 BID for 14 to 28 days.

35. The method according to claim 33 or 34, comprising administering to the human patient a first dose of 400 mg of PRN1008 BID for 22 days.

36. The method according to claim 33, comprising administering to the human patient a first dose of 400 mg of PRN1008 BID for more than 28 days.

37. The method according to claim 33 or 36, comprising administering to the human patient a first dose of 400 mg of PRN1008 BID for 56 days.

38. The method according to any of claims 33 to 37, wherein PRN1008 is administered to the human patient for a maximum of 84 days.

39. The method according to claim 18, comprising: administering to the human patient a first dose of 400 mg of PRN1008 BID for at least 14 days; administering to the human patient a second dose of 500 mg of PRN1008 BID for at least 14 days after the administration of the first dose; and administering to the human patient a third dose of 600 mg of PRN1008 BID after the administration of the second dose.

40. The method according to claim 39, comprising administering to the human patient a first dose of 400 mg of PRN1008 BID for 14 to 28 days.

41. The method according to claim 39 or 40, comprising administering to the human patient a second dose of 500 mg of PRN1008 BID for 14 to 28 days after administration of the first dose.

42. The method according to any of claims 39 to 41, wherein PRN1008 is administered to the human patient for a maximum of 84 days.

43. The method according to any one of claims 1 to 42, comprising administering PRN1008 in combination with a first corticosteroid at a dose of less than or equal to 0.5 mg / kg / day. pozfrnn / zznz / E / YiAi 44. The method according to claim 43, wherein the first corticosteroid is selected from prednisone, prednisolone, and methylprednisolone.

45. The method according to any of claims 1 to 44, wherein the human patient is characterized by untreated or relapsing pemphigus prior to administration of PRN1008.

46. ​​The method according to any of claims 1 to 45, wherein the human patient is characterized by untreated or relapsing pemphigus vulgaris prior to administration of PRN1008.

47. The method according to any of claims 1 to 46, wherein the human patient is characterized by untreated or relapsing pemphigus foliaceus prior to administration of PRN1008.

48. The method according to any of claims 1 to 47, wherein the human patient is characterized by a Pemphigus Disease Activity Index (PDAI) skin score of 8 points to 60 points prior to administration of PRN1008.

49. The method according to any of claims 1 to 48, wherein the human patient is characterized by a maintenance dose of less than or equal to 0.5 mg / kg / day of a second corticosteroid prior to the administration of PRN1008.

50. The method according to claim 49, wherein the second corticosteroid is selected from prednisone, prednisolone, and methylprednisolone.

51. The method according to claim 49 or 50, wherein the first corticosteroid is the same as the second corticosteroid.

52. The method according to claim 49 or 50, wherein the first corticosteroid is not the same as the second corticosteroid.

53. The method according to any of claims 1 to 52, wherein PRN1008 comprises the isomer (E) of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)prazolo[3,4-d]primidin-11l]piperidin-1-carbonyl]-4-methyl-4-[4-(oxetan-3-11)piperazin-1-11]pent-2-enenitrol.

54. The method according to any of claims 1 to 52, wherein PRN1008 comprises the isomer (Z) of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)prazolo[3,4-d]pyrimidin-1-1]piperidin-1-carbonyl]-4-methyl-4-[4-(oxetan-3-1-1)piperazin-1-1-1]pent-2-enonitrile.

55. The method according to any of claims 1 to 52, wherein PRN1008 comprises a mixture of the (E) and (Z) isomers of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1 -yl]piperidine-1 -carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazín-1 -yl]pent-2enenitrile.

56. The method according to any of claims 1 to 55, comprising treating pemphigus vulgaris.

57. The method according to any of claims 1 to 55, comprising treating pemphigus foliaceus.

58. The method according to any of claims 1 to 57, comprising reducing the average daily use of corticosteroids by the human patient.

59. The method according to claim 58, comprising reducing the average daily use of corticosteroids by the human patient by at least 20%. rozfrnn / zznz / E / YiAi 60. The method according to claim 58, comprising reducing the average daily use of corticosteroids by the human patient by at least 50%.

61. The method according to any one of claims 1 to 60, comprising curing established lesions of pemphigus.

62. The method according to claim 61, comprising curing at least 50% of established pemphigus lesions.

63. The method according to any of claims 1 to 62, comprising preventing the formation of new pemphigus lesions.

64. The method according to any of claims 1 to 63, comprising reducing a skin score of the Pemphigus Disease Activity Index (PDAI).

65. The method according to claim 64, comprising reducing a PDAI skin score by at least 20%.

66. The method according to any of claims 1 to 64, wherein the human patient is characterized by a Pemphigus Disease Activity Index (PDAI) skin score of 0 or 1 after administration of PRN1008.

67. The method according to claim 66, wherein the human patient is characterized by a PDAI skin score of 0 after administration of PRN1008.

68. The method according to claim 66, wherein the human patient is characterized by a PDAI skin score of 1 after administration of PRN1008.

69. The method according to any of claims 1 to 60, further comprising achieving control of pemphigus disease activity.

70. The method according to any of claims 1 to 60, further comprising achieving an end to the pemphigus consolidation phase.

71. The method according to claim 70, wherein more than 60% of the established pemphigus lesions have been cured.

72. The method according to any of claims 1 to 60, comprising achieving a complete remission.

73. The method according to any of claims 1 to 72, wherein PRN1008 is administered orally to the human patient.

74. The method according to any of claims 1 to 73, wherein PRN1008 is administered to the human patient in the form of at least one tablet.

75. The method according to claim 74, wherein PRN1008 is administered with a glass of water.

76. The method according to any of claims 1 to 75, wherein PRN1008 is administered with food.

77. The method according to any of claims 1 to 75, wherein PRN1008 is administered without food.