TREATMENT OF CUTANEOUS LUPUS ERYTHEMATOSUS

Abstract

The present invention relates to the treatment of cutaneous lupus erythematosus. The problem to be solved by the invention is to provide a new pharmaceutical use for 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3,4]octan-1-yl]-3-oxopropanenitrile. A therapeutic or preventive agent for cutaneous lupus erythematosus, containing 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3,4]octan-1-yl]-3-oxopropanenitrile as an active ingredient and a pharmaceutical formulation thereof.

Description

The present invention relates to a novel pharmaceutical use of delgocitinib, 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile. In another aspect, the present invention relates to the treatment of cutaneous lupus erythematosus. In yet another aspect, the present invention relates to a novel topical pharmaceutical formulation comprising delgocitinib. BACKGROUND OF THE INVENTION Lupus erythematosus is an inflammatory autoimmune disease that can affect only the skin (cutaneous lupus erythematosus, CLE) but can also involve severe systemic organ involvement (systemic lupus erythematosus, SLE). CLE can be acute, subacute, or chronic. Discoid lupus erythematosus (DLE) is the most common form of chronic CLE, accounting for 80% of all cases. Discoid lupus erythematosus (DLE) is an autoimmune disease that affects the skin with localized, scaly, erythematous lesions. Over time, these lesions can cause scarring, atrophy, depigmentation, and hair loss. DLE lesions typically vary in size, ranging from a few millimeters to 15 centimeters in diameter, and are primarily found in areas exposed to UV radiation, such as the Ref. 326689 head and neck, and to a lesser extent the trunk and limbs. Physical appearance affects the quality of life of patients with LDE and is associated with a higher risk of depression and unemployment. LED is classified as localized (only lesions above the neck) or generalized (lesions both above and below the neck), the localized form being much more common. Currently, there is no cure for LDE, and no treatments have been approved for this condition. Current and usual care treatments are used off-label and have limited effect. First-line treatment recommendations include sun avoidance, UV protection, and potent topical corticosteroids. Several JAK inhibitors are in clinical development or are already on the market. Ruxolitinib, the first JAK1 and JAK2 inhibitor approved by the FDA, is an oral medication approved in several countries / regions for the treatment of patients with myelofibrosis. Tofacitinib is currently approved in the US as an oral medication for the treatment of rheumatoid arthritis and is currently in development for the treatment of psoriasis and atopic dermatitis. Patent WO2011 / 013785 describes nitrogen-containing spirocyclic compounds and their pharmaceutical uses. It states that the compounds are JAK inhibitors useful for the prevention or treatment of, for example, autoimmune diseases, allergic diseases, psoriasis, rheumatoid arthritis, and atopic dermatitis. Patent EP 2813228 Al describes the pharmaceutical use of a JAK inhibitor, and more specifically a pharmaceutical composition for the treatment of skin diseases such as senile xerosis, asteatosis, eczema and contact dermatitis. fr / ozLn / ίζηζ / Β / γι Consequently, there is an unmet medical need for a new treatment for cutaneous lupus erythematosus that is highly effective in combination with an attractive safety profile. Currently there is an ointment formulation, which is a paraffin-based formulation containing Delgocitinib in suspended solid form. Surprisingly, a stable cream formulation has been obtained with Delgocitinib dissolved in the aqueous phase. BRIEF DESCRIPTION OF THE INVENTION The present invention relates to the treatment of cutaneous lupus erythematosus comprising the compound with formula (I) 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3d]pyrimidin-4-yl)-1,6diazaspiro[3,4]octan-l-yl]-3-oxopropanonitrile, or a pharmaceutically acceptable salt thereof. In one aspect, the present invention relates to the use of the compound with formula (I) for use in the treatment of cutaneous lupus erythematosus. In another aspect of the present invention, it refers to the use of the compound with formula (I) for use in the treatment of discoid lupus erythematosus. In another aspect, the present invention relates to the use of the compound of formula (I) for the treatment of cutaneous lupus erythematosus. In yet another aspect, the invention relates to the compound of formula (I) for use in the treatment of discoid lupus erythematosus. In yet another aspect, the invention relates to the compound of formula (I) for use in the treatment of cutaneous lupus erythematosus, for example, discoid lupus erythematosus. In yet another aspect, the topical formulation is a cream. In yet another aspect, the present invention relates to the use of the compound of formula (I), which is administered once or twice daily. In yet another aspect, the present invention relates to the use of the compound of formula (I), which is administered twice daily for 6 weeks. In yet another aspect, the present invention relates to the compound of formula (I), which is administered at a concentration of 20 mg / g. fr / ozLn / Lznz / E / Yii In another aspect, the present invention relates to the use of the compound of formula (I) in the manufacture of a pharmaceutical composition for the treatment of cutaneous lupus erythematosus, for example, discoid lupus erythematosus. In yet another aspect, the pharmaceutical composition is a topical formulation. In yet another aspect, the topical formulation is a cream. In another aspect, the present invention relates to a pharmaceutical composition comprising a compound with the formula (I) fr / ozLn / Lznz / E / Yii 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3d]pyrimidin-4-yl)-1,6diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile, or a pharmaceutically acceptable salt thereof, for the treatment of cutaneous lupus erythematosus. In another aspect, the present invention refers to the pharmaceutical composition for the treatment of discoid lupus erythematosus. In another aspect, the present invention refers to the pharmaceutical composition comprising the compound with formula (I), wherein the treatment is topical, for example, a treatment with a cream. In another aspect, the present invention relates to the pharmaceutical composition, wherein the compound of formula (I) is administered at a concentration of 1 mg / g, 3 mg / g, 8 mg / g, and 20 mg / g. In another aspect, the compound of formula (I) is administered at a concentration of 20 mg / g. In another aspect, the compound of formula (I) is administered as a once- or twice-daily application. In another aspect, the compound of formula (I) is administered as a twice-daily application for 6 weeks. In another aspect, the present invention relates to a method for treating cutaneous lupus erythematosus, for example, discoid lupus erythematosus, in a subject who needs it, the method comprising the step of administering to the subject a therapeutically effective amount of the compound with formula (I). In another aspect, the present invention relates to a method for treating cutaneous lupus erythematosus, for example, discoid lupus erythematosus, in a subject who needs it, where the administration is topical. In another aspect, the present invention relates to a method for treating cutaneous lupus erythematosus, for example, discoid lupus erythematosus, in a subject who needs it, where the topical formulation is a cream. In another aspect, the present invention relates to a method for treating cutaneous lupus erythematosus, for example, discoid lupus erythematosus, in a subject in need, wherein the compound of formula (I) is administered at a concentration of 1 mg / g, 3 mg / g, 8 mg / g, and 20 mg / g. In another aspect, the compound of formula (I) is administered at a concentration of 20 mg / g. The present invention also provides for the use of 3[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile in the treatment of cutaneous lupus erythematosus. The present invention further provides the above use administered as a once-daily or twice-daily application. The present invention further provides the aforementioned use administered at a concentration of 1 mg / g, 3 mg / g, 8 mg / g, and 20 mg / g. DETAILED DESCRIPTION OF THE INVENTION fr / ozLn / Lznz / E / Yii The compound with formula (I) 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3d]pyrimidin-4-yl)-1,68 diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile, was previously described in patent WO2011 / 013785 as a JAK inhibitor for the treatment of, for example, autoimmune diseases, allergic diseases, psoriasis, rheumatoid arthritis and atopic dermatitis, and in patent EP 2813228 Al for the treatment of skin diseases such as senile xerosis, asteatosis, eczema and contact dermatitis. The compound with formula (I) can be produced according to the method described in Preparation 6 of patent WO2011 / 013785. The "pharmaceutically acceptable salt" can be any nontoxic salt of the compound with formula (I), and includes a salt with an inorganic acid, a salt with an organic acid, a salt with an inorganic base, a salt with an organic base, and a salt with an amino acid. Salts containing inorganic acids include salts containing hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, hydrobromic acid, etc. Salts containing organic acids include salts containing oxalic acid, maleic acid, citric acid, fumaric acid, lactic acid, malic acid, succinic acid, tartaric acid, acetic acid, trifluoroacetic acid, citric acid monohydrate, gluconic acid, ascorbic acid, methanesulfonic acid, benzenesulfonic acid, ptoluenesulfonic acid, etc. Salts containing inorganic bases include sodium salts, potassium salts, calcium salts, magnesium salts, ammonium salts, etc. Salt with an organic base includes salt with methylamine, diethylamine, trimethylamine, triethylamine, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, tris(hydroxymethyl)methylamine, dicyclohexylamine, N,N'dibenzylethylenediamine, guanidine, pyridine, picoline, choline, cinchonine, meglumine, etc.A salt containing an amino acid includes a salt containing lysine, arginine, aspartic acid, glutamic acid, etc. According to well-known methods, each salt can be obtained by reacting the compound with formula (I) with an inorganic base, an organic base, an inorganic acid, an organic acid, or an amino acid. The compound with formula (I) can be labeled with isotopes, for example, qC, °S. In one respect, the compound of formula (I) or a pharmaceutically acceptable salt thereof is the substantially purified compound of formula (I) or a pharmaceutically acceptable salt thereof. In another respect, the compound of formula (I) or a pharmaceutically acceptable salt thereof has a purity of 80% or more. The term "pharmaceutical composition" includes a preparation for oral use, such as a tablet, capsule, granule, powder, lozenge, syrup, emulsion, or suspension, or a parenteral preparation, such as a topical agent, suppository, injection, eye drops, nasal spray, or pulmonary drug. In another sense, a pharmaceutical composition is a topical formulation, such as an ointment or cream. In yet another sense, a pharmaceutical composition is a cream. The pharmaceutical composition of the present invention is produced by suitably mixing the compound with formula (I) or a pharmaceutically acceptable salt thereof, with at least one type of pharmaceutically acceptable excipient or vehicle in sufficient quantities according to methods known in the technical field of medical preparation. The content of the compound with formula (I) or a pharmaceutically acceptable salt thereof in the pharmaceutical composition depends on its pharmaceutical forms, dosage amounts, etc., and, for example, ranges from 0.1 to 100% by weight of the complete composition. For example, the content is 0.10, 0.20, 0.25, 0.30, 0.50, 0.75, 1.0, 1.25, 1.50, 1.75, 2.00, 2.25, 2.50, 2.75, 3.00, 3.25, 3.50, 3.75, or 4.00% by weight of the entire composition. In another respect, the content of the compound with formula (I) or a pharmaceutically acceptable salt thereof in the pharmaceutical composition is 2% by weight of the complete composition. The term “therapeutically effective amount” of the compound as used herein means an amount sufficient to cure, alleviate, or partially halt the clinical manifestations of a given disease and its complications. An amount adequate to achieve this is defined as a “therapeutically effective amount.” Effective amounts for each purpose will depend on the severity of the disease or injury as well as the weight and general condition of the subject. A "pharmaceutically acceptable excipient" or "pharmaceutically acceptable vehicle" includes various conventional organic or inorganic excipients or carriers for pharmaceutical materials, such as a disintegrant, binder, fluidifier, lubricant, solvent, solubilizer, suspending agent, tonicity agent, buffer, and soothing agent for liquid preparations, and a base, emulsifier, surfactant, humectant, stabilizer, stabilizing agent, dispersant, plasticizer, pH regulator, absorption promoter, gelling agent, antiseptic, filler, or resolvent. Additionally, an additive may be used, including a preservative, antioxidant, and colorant, if required. The disintegrant includes carmellose, calcium carmellose, sodium carmellose, sodium carboxymethyl starch, croscarmellose sodium, crospovidone, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, crystalline cellulose, fr / ozLn / Lznz / E / Yii etc. The binder includes hydroxypropylcellulose, hydroxypropylmethylcellulose, povidone, crystalline cellulose, white soft sugar, dextrin, starch, gelatin, sodium carboxymethylcellulose, gum arabic, etc. The fluidizer includes light anhydrous silicic acid, magnesium stearate, etc. The lubricant includes magnesium stearate, calcium stearate, talc, etc. The solvent includes purified water, ethanol, propylene glycol, macrogol, sesame oil, corn oil, olive oil, medium-chain triglycerides, etc. The solubilizing agent includes propylene glycol, mannitol D, benzyl benzoate, ethanol, triethanolamine, sodium carbonate, sodium citrate, etc. The suspending agent includes benzalkonium chloride, carmellose, hydroxypropylcellulose, propylene glycol, povidone, methylcellulose, glyceryl monostearate, etc. The tonic agent includes glucose, sorbitol D, sodium chloride, mannitol D, etc. The pH buffer or regulator includes phosphate or citrate salts, sodium hydrogen phosphate, sodium acetate, sodium carbonate, sodium citrate, sodium citrate dihydrate, citric acid monohydrate, hydrochloric acid, sodium hydroxide, etc. The base includes water, animal or vegetable oils (for example, olive oil, corn oil, peanut oil, sesame oil, castor oil, safflower oil, etc.), lower alcohols (for example, ethanol, propanol, propylene glycol, 1,3-butylene glycol, phenol, etc.), higher fatty acids and their esters, waxes, higher alcohols, polyhydric alcohols, hydrocarbons (for example, white soft paraffin, liquid paraffin, paraffin, hard paraffin, etc.), hydrophilic petrolatum, purified lanolin, absorbent ointment, hydrated lanolin, hydrophilic ointment, starch, pullulan, polydimethylsiloxane, isopropyl myristate, gum arabic, tragacanth gum, gelatin, dextran, cellulose derivatives (for example, For example, methylcellulose, carboxymethylcellulose, hydroxyethyl (e.g., carboxyvinyl polymer, sodium polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, etc.), propylene glycol, macrogol (e.g., macrogol 200 to 600, etc.).) and combinations of two or more of these types. In one aspect, the base is liquid paraffin. The emulsifier or surfactant includes mixtures of fatty acids, especially cetyl alcohol, stearyl alcohol and cetostearyl alcohol, macrogol cetostearyl ether, sorbitan esters, sucrose esters, etc. The stabilizer includes sucrose esters, other sorbitan esters and polysorbates, glycol, propylene glycol, ethanol, cetostearyl alcohol, etc. fr / OZLÍV ί7Π7 / Β / ΥΙ The acidifying agent includes a strong acid that is selected from, for example, hydrochloric acid or citric acid. The chelating agent includes ethylenediaminetetraacetic acid (EDTA), disodium edetate, ethylene glycol tetraacetic acid (EGTA), ethylenediamine, phosphoric acid, etc. The preservative includes ethyl parahydroxybenzoate, chlorobutanol, benzyl alcohol, sodium dehydroacetate, sorbic acid, chlorocresol, dichlorobenzyl alcohol, glycerol, ethanol, propylene glycol, benzoic acid / sodium benzoate, diazolidinurea, benzalkonium chloride, etc. The antioxidant includes sodium sulfite, ascorbic acid, disodium edetate, trisodium edetate, alpha-tocopherol, butylated hydroxyanisole, etc. The colorant includes food coloring, β-carotene, etc. The pharmaceutical composition of the present invention can be administered to a mammal, such as a human. The dosage amount depends on the subject, disease, symptoms, pharmaceutical form, route of administration, etc., and may be in the range of approximately 0.01 mg to approximately 1 g, for example, from approximately 0.01 mg to approximately 600 mg per day in terms of the content of the compound with formula (I) as the active ingredient. The dose can be administered all at once or in several divided doses. A topical agent can be applied, for example, by application, ointment, or spray, depending on the pharmaceutical form, etc. The amount of the topical agent applied to the affected area can be selected based on the active ingredient content, etc., and the topical agent can be applied, for example, all at once or in several divided amounts throughout the day. Once or twice daily application is preferred. The phrase "JAK" refers to one or more of the JAK1, JAK2, JAK3, and TYK2 enzymes that belong to the JAK family. The phrase "JAK inhibition" refers to inhibiting JAK functions to eliminate or attenuate their activity, and to inhibiting one or more enzymes belonging to the JAK family. In one sense, the phrase "JAK inhibition" refers to "inhibiting human JAK." The inhibition of functions or the elimination or attenuation of activity is, in one sense, carried out in situations of human clinical application. The term “JAK inhibitor” can refer to any substance that inhibits JAK and may include, for example, low molecular weight compounds, nucleic acids, polypeptides, proteins, antibodies, vaccines, etc. In one sense, “JAK inhibitor” refers to a “human JAK inhibitor.” In another sense, the JAK inhibitor is the compound with formula (I) or a pharmaceutically acceptable salt thereof. In yet another sense, the JAK inhibitor is the compound with formula (I). The term "treatment," as used in this description, includes symptom improvement, prevention of aggravation, maintenance of remission, prevention of exacerbation, and prevention of recurrence. The term "prevention" refers to suppressing the occurrence of a symptom. The term "treatment" may also include slowing the progression of the disease, disorder or condition, improving, relieving or compensating for symptoms and complications, and / or curing or eliminating the disease, disorder or condition. The term "treatment" can also mean the treatment and care of a patient for the purpose of combating disease, condition, or disorder. The terms "disease," "disorder," and "condition," as used in this description, are used interchangeably to specify a patient's condition that is not the normal physiological state of a human being. The term "cutaneous lupus erythematosus (CLE)" can also include acute cutaneous lupus erythematosus, such as lupus vespertilius, photosensitivity reactions, and mucosal lupus erythematosus erosions. CLE can also include subacute cutaneous lupus erythematosus (SCLE), such as papulosquamous SCLE (also known as psoriasiform SCLE), the annular variant of SCLE, and Rowell syndrome. Additionally, CLE can also include chronic cutaneous lupus erythematosus (CCLE), such as discoid lupus erythematosus (DLE), lupus tumidus, lupus profundus, hypertrophic and deep lupus, and perniotic lupus. One embodiment of the present invention includes a pharmaceutical composition for treating or preventing cutaneous lupus erythematosus, for example, discoid lupus erythematosus, comprising 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3d]pyrimidin-4-yl)-1,6-diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile and a pharmaceutically acceptable excipient or vehicle. One embodiment of the present invention includes the use of 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile to treat or prevent cutaneous lupus erythematosus, for example, discoid lupus erythematosus. One embodiment of the present invention includes a method for treating or preventing cutaneous lupus erythematosus, for example, discoid lupus erythematosus, characterized by administering to a mammal a therapeutically effective amount of 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile. In one respect, the mammal is a human being. In another aspect, a human being is a person who suffers from a disease and needs medical attention. In another aspect, the disease is cutaneous lupus erythematosus. In another aspect, the disease is acute cutaneous lupus erythematosus, such as lupus vesertilia, photosensitivity reaction, and mucosal lupus erythematosus erosions. In another aspect, the disease is subacute cutaneous lupus erythematosus (SCLE), such as papulosquamous SCLE, annular variant of SCLE, and Rowell syndrome. In another aspect, the disease is chronic cutaneous lupus erythematosus, such as discoid lupus erythematosus (DLE), lupus tumidus, lupus profunda, hypertrophic lupus profundus, and lupus pernioticus. In another aspect, the disease is discoid lupus erythematosus (DLE). In another aspect, the present invention relates to a therapeutic or preventive agent for cutaneous lupus erythematosus, for example, discoid lupus erythematosus, comprising the compound with formula (I). In another respect, the present description refers to a pharmaceutical composition comprising a compound with formula (I) and a pharmaceutically acceptable excipient or carrier. In another aspect, the present invention relates to a pharmaceutical formulation for topical administration, comprising the compound with formula (I) and one or more pharmaceutically acceptable excipients. In another aspect, the present invention relates to a pharmaceutical formulation that is a cream, comprising the compound with formula (I) and one or more pharmaceutically acceptable excipients. In another respect, a pharmaceutically acceptable excipient could be one or more bases selected from medium-chain triglycerides, safflower oil, castor oil, liquid paraffin, or mixtures thereof. For example, the base could be liquid paraffin. The base could be present in various amounts from approximately 50 mg / g to approximately 500 mg / g of liquid paraffin, for example, from approximately 75 mg / g to approximately 300 mg / g, for example, 100 mg / g. In another respect, a pharmaceutically acceptable surfactant, emulsifier, or stabilizer could be one or more of the following selected from cetyl alcohol, stearyl alcohol, cetostearyl alcohol, or mixtures thereof. For example, the surfactant, emulsifier, or stabilizer could be cetostearyl alcohol. The surfactant, emulsifier or stabilizer could be present in various amounts from approximately 20 mg / g to approximately 100 mg / g of cetostearyl alcohol, for example, from approximately 40 mg / g to approximately 80 mg / g, for example, 72 mg / g. In another respect, a pharmaceutically acceptable surfactant, emulsifier, or stabilizer could be one or more of the following selected from sorbitan esters, macrogol cetostearyl ether, or mixtures thereof. For example, the surfactant or emulsifier could be cetostearyl alcohol. The surfactant, emulsifier, or stabilizer could be present in various amounts, from approximately 9 mg / g to approximately 25 mg / g of macrogol cetostearyl ether, for example, from approximately 15 mg / g to approximately 20 mg / g, and, for example, 18 mg / g. In another respect, a pharmaceutically acceptable pH buffer or regulator could be one or more of a phosphate or citrate salt, sodium acetate, sodium carbonate, sodium citrate dihydrate, hydrochloric acid, or mixtures thereof. For example, the pH buffer or regulator could be one or more of citric acid monohydrate and sodium citrate dihydrate. The pH buffer or regulator could be present in various amounts, from approximately 0.5 mg / g to approximately 4 mg / g of citric acid monohydrate, for example, from approximately 0.7 mg / g to approximately 2 mg / g, and for example, 1 mg / g. The pH buffer or regulator could be present in various amounts, from approximately 0 mg / g to approximately 1 mg / g of sodium citrate monohydrate, for example, from approximately 0 mg / g to approximately 0.5 mg / g, and, for example, absent. fr / ozLn / ίζηζ / Β / γι In another respect, a pharmaceutically acceptable preservative could be one or more of the following: benzyl alcohol, sodium dehydroacetate, sorbic acid / salts, or mixtures thereof. For example, the preservative could be benzyl alcohol. The preservative could be present in varying amounts, from approximately 7 mg / g to approximately 13 mg / g of benzyl alcohol, for example, from approximately 9 mg / g to approximately 11 mg / g, for example, 10 mg / g. In another respect, a pharmaceutically acceptable antioxidant could be one or more of the following selected from sodium sulfite, disodium edetate, trisodium edetate, butylated hydroxyanisole, or mixtures thereof. For example, the antioxidant could be butylated hydroxyanisole. The antioxidant could be present in various amounts, from approximately 0.05 mg / g to approximately 0.3 mg / g of butylated hydroxyanisole, for example, from approximately 0.1 mg / g to approximately 0.25 mg / g, for example, 0.2 mg / g. In another respect, a pharmaceutically acceptable chelating agent could be one or more of EDTA, disodium edetate, EGTA, or ethylenediamine. For example, the chelating agent could be disodium edetate. The chelating agent could be present in various amounts of between approximately 0.05 mg / g and approximately 1.5 mg / g of disodium edetate, for example, between approximately 0.5 mg / g and approximately 1 mg / g, for example, 0.6 mg / g. In another respect, a pharmaceutically acceptable acidifying agent could be one or more strong acids, for example, hydrochloric acid or citric acid. For example, the acidifying agent could be hydrochloric acid. The acidifying agent could be present in various amounts from 0 mg / g to approximately 25 mg / g of hydrochloric acid, for example, from approximately 10 mg / g to approximately 20 mg / g, for example, 17.7 mg / g. In another respect, a pharmaceutically acceptable solvent could be purified water, which could be present in various amounts from approximately 500 mg / g to approximately 900 mg / g, for example, 760 mg / g. In another aspect, the present invention relates to a method for preparing the present pharmaceutical formulation, where The aqueous phase: Purified water, pH regulators, buffers, acidifying agents, preservatives, and chelating agents were mixed together. The pharmaceutical substance was added and dissolved in the aqueous phase at a temperature of around 15 °C to 25 °C. fr / OZLÍV ί7Π7 / Β / ΥΙ The pH was adjusted to 4.0-4.4. The aqueous phase was heated to around 65°C to 75°C. The oily phase: Liquid paraffin, surfactants, emulsifiers, stabilizers, and antioxidants were mixed. The aqueous phase was heated to around 65°C to 75°C. The oil phase was added to the aqueous phase and mixed. The mixture was homogenized for approximately 20 minutes and then cooled to approximately 30°C. The container was then sealed and filled with cream. Example pharmaceutical formulations of the present invention: Amount of component (mg / g): Delgocitinib 1; liquid paraffin 100; cetostearyl alcohol 72; macrogol cetostearyl ether 18; benzyl alcohol 10; citric acid monohydrate 0.78; butylated hydroxyanisole 0.2; disodium edetate 0.6; sodium citrate dihydrate 0.31 and purified water 797. Component quantity (mg / g): Delgocitinib 3; liquid paraffin 100; cetostearyl alcohol 72; macrogol cetostearyl ether 18; benzyl alcohol 10; citric acid monohydrate 1.0; butylated hydroxyanisole 0.2; disodium edetate 0.6; 3M hydrochloric acid 1.08 and purified water 794. Component quantity (mg / g): Delgocitinib 8; liquid paraffin 100; cetostearyl alcohol 72; macrogol cetostearyl ether 18; benzyl alcohol 10; citric acid monohydrate .0; butylated hydroxyanisole 0.2; disodium edetate 0.6; 3M hydrochloric acid 6.43 and purified water 784. Component quantity (mg / g): Delgocitinib 20; liquid paraffin 100; cetostearyl alcohol 72; macrogol cetostearyl ether 18; benzyl alcohol 10; citric acid monohydrate 1.0; butylated hydroxyanisole 0.2; disodium edetate 0.6; 3M hydrochloric acid 17.7 and purified water 760. In another aspect, the present invention relates to a pharmaceutical composition comprising a compound with formula (I) and excipients as described in the investigational product (IP-1). In another aspect, the present invention relates to a pharmaceutical formulation for topical administration comprising the compound with formula (I) and the excipients as described in the investigational product (IP-2). The present invention describes its effect in the topical treatment of cutaneous lupus erythematosus. In another aspect, the present invention describes its effect in the topical treatment of discoid lupus erythematosus. The present invention provides a clinical trial to compare the efficacy and safety of twice-daily topical application of a 20 mg / g cream of the compound with formula (I), with a cream vehicle, for 6 weeks in the treatment of adult subjects with cutaneous lupus erythematosus, more specifically discoid lupus erythematosus. All subjects will receive active treatment in one target lesion of cutaneous lupus erythematosus and vehicle treatment in another target lesion of cutaneous lupus erythematosus. The following has been defined as a measure of effectiveness and safety: Efficacy assessments are the Investigator Global Assessment (IGA) of the severity of each target lesion (score of 0 (cured) or 1 (almost cured) at week 6) and the skin lesion activity and damage scores (erythema, scaling / hyperkeratosis, edema / infiltration, depigmentation, scarring / atrophy) (according to the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI)) for each target lesion. For details on the IGA and RCLASI, see below. Subject assessments of efficacy and health-related quality of life are based on the Patient Global Assessment (PaGA) of the severity of each target lesion and the Dermatologic Life Quality Index (DLQI). EXAMPLES Clinical trial The clinical trial is a phase 2a, multicenter, double-blind, randomized, vehicle-controlled trial in adult subjects with fr / ozLn / Lznz / E / Yii using twice-daily topical application of the compound with formula (I), formulated as a cream, 20 mg / gy vehicle cream for 6 weeks. Each subject must have at least 2 target LED lesions with active disease. The 2 target lesions will be randomly assigned 1:1 to active and vehicle treatment. Treatment period At the start of the study (Day 1), the treatment allocation for the two target lesions will be randomly assigned (1:1) to the 20 mg drug cream / vessel. The treatment will be applied twice daily for 6 weeks. The first application of the investigational medicinal product (IMP) will take place at the trial site on Day 1, after all baseline assessments have been completed. Subsequent IMP applications will be performed by the patients at home. During the 6-week treatment period, subjects will return to the trial site for scheduled visits in weeks 2, 4, and 6. The final application of the IMP will occur on the night before subjects attend their scheduled visit in week 6. Main inclusion criteria: - Age: from 18 to 70 years. - Histopathological findings (current or previous) compatible with the clinical diagnosis of fr / OZLÍV ί7Π7 / Β / YΙ LED. - Unequivocal clinical diagnosis of two active LED target lesions that are < 6 months old and amenable to clinical assessment. This includes lesions located on the scalp if they meet all lesion-specific eligibility criteria. - Target lesion IGA score of at least moderate (IGA >3) at screening and baseline. - A difference of 1 point in the IGA score between the 2 target injuries at selection and at the start. - Target lesion erythema score >2 at screening and baseline. Main exclusion criteria: - Target lesion depigmentation score of 2 at screening or baseline. - Target lesion healing / atrophy score of 2 at screening or baseline. Target lesion scarring alopecia score > 0 at screening or baseline. - Clinical history of SLE with clinically significant organ involvement, including SLE-related pleuritis or pericarditis, and neurological, renal, and / or other SLE-related organ system involvement. Joint involvement of SLE is acceptable. fr / OZLÍV ί7Π7 / Β / ΥΙ - Subjects with unstable or significant SLE disease activity according to the researcher's experience. Other skin conditions at the time of selection or at the start that could interfere with the LED assessment. - Immunosuppressive / immunomodulatory therapy, for example, methotrexate, cyclosporine, azathioprine, retinoids, dapsone in the 4 weeks prior to initiation. - Systemic prednisolone > 7.5 mg / day or modified dose in the 4 weeks prior to initiation (nasal and inhaled corticosteroids are permitted). - Treatment with the following medications: Oral antimalarial treatment with hydroxychloroquine > 6.5 mg / kg body weight / day, or chloroquine > 4 mg / kg body weight / day, or modified dose in the 12 weeks prior to initiation. Quinacrine combined with hydroxychloroquine or chloroquine in the 12 weeks prior to initiation. Medications known to interact with antimalarials (e.g., digoxin, cimetidine) in the 12 weeks prior to initiation. - Treatment with topical corticosteroids, calcineurin inhibitors, and phosphorus-diesterase-4 (PDE4) inhibitors in the 2 weeks prior to initiation. fr / OZLÍV ί7Π7 / Β / ΥΙ - Use of systemic antibiotics or antibiotics applied topically to the target lesions in the 2 weeks prior to onset. UV treatment in the 2 weeks prior to the start. - Any procedure affecting the skin barrier (e.g., incision) within 2 cm of the edge of any of the target lesions in the 4 weeks prior to initiation. - Receipt of live (attenuated) vaccines in the 4 weeks prior to the start. - Products containing Hypericum perforatum (St. John's wort) in the 4 weeks prior to the start. Treatment with any commercially available biological therapy or investigational biological agents: Any cell-depleting agent, including but not limited to rituximab: in the 6 months prior to baseline, or until lymphocyte count returns to normal, whichever is longer. Other biologicals: within 3 months or 5 half-lives, whichever is longer, before the start. - History of any active skin infection in the week 1 prior to onset. - Clinically significant infection in the 4 weeks prior to the start of the trial that, in the investigator's opinion, may compromise the subject's safety in the trial. fr / ozLn / Lznz / E / Yi - Tuberculosis requiring treatment in the 12 months prior to screening and / or subjects with a positive blood test for tuberculosis at screening. Investigator Global Assessment (IGA) for discoid lupus erythematosus (DLE) The IGA is used to rate the overall severity of the subject's disease and is based on a 5-point scale ranging from 0 (cured) to 4 (severe). The investigator will use the IGA as a lesion-specific assessment to rate the severity of the LED for each of the two target lesions separately. fr / ozLn / Lznz / E / Yii Investigator Global Assessment (IGA) for discoid lupus erythematosus (DLE) Disease Severity Score Morphological Description 0 Normal No signs of SLE activity (no erythema, no scaling / hyperkeratosis, no edema / infiltration). There may be signs of damage (depigmentation and / or scarring and atrophy). 1 Near normal Only pink or mild erythema. No scaling / hyperkeratosis or edema / infiltration. 2 Mild Only pink or mild erythema. Mild scaling (mainly fine scales) and / or mild dermal edema. 3 Moderate Prominent erythema. Mild scaling (mainly fine to circumscribed scales) and / or mild or determined dermal edema. 4 Severe. Prominent red, dark red, violet, or purplish color. Crusting may be present. Severe scaling with follicular plugging and / or dermal edema with induration of the skin. fr / ozLn / Lznz / E / Yi Revised Cutaneous Lupus Erythematosus Disease Severity and Area Index (RCLASI) The RCLASI is a validated scoring system for assessing disease activity and damage in patients with CLE, taking into account both anatomical region and morphological aspects. The RCLASI skin lesion activity and damage sign scores apply only to the targeted lesions. The scores and the sum of the individual signs will provide a quantitative assessment of the treatment effect. A high RCLASI score indicates more severe disease. In addition, a comprehensive RCLASI assessment will be performed at baseline to describe the overall disease burden of cutaneous lupus erythematosus (CLE) in the trial population. The total skin disease activity score is defined as the sum of the erythema, scaling / hyperkeratosis, and edema / infiltration scores: Erythema: 0 = Absent; 1 = Pink, faint; 2 = Red; 3 = Dark red, violet / purple / crusted / hemorrhagic. Scaling / hyperkeratosis: 0 = Absent; 1 = Circumscribed adherent scaling / follicular plugging; Verrucous hyperkeratosis. Edema / infiltration: 0 = Absent; 1 = Slight, simply palpable; 2 = Palpable and visible. The total skin disease damage score is defined as the sum of the depigmentation and scarring / atrophy scores: Dispigmentation: 0 = Absent; 1a = Hypopigmentation; 1b = Hyperpigmentation; 2 = Hypo and hyperpigmentation. Scarring / atrophy: 0 = Absent; 1 = Initial scarring; 2 = Firm / atrophic / severe vermicular scarring. Patient Global Assessment of Disease Severity (PaGA) The PaGA is a self-assessment of subjects' perception of the severity of the disease. The subjects will assess the severity of the disease for each target lesion using the PaGA. The assessment will be performed using the 5-point scale: = Normal; 1 = Almost normal; 2 = Mild; 3 = Moderate; 4 = Severe. Dermatology Life Quality Index (DLQI) The DLQI is a validated questionnaire with content specifically designed for people with dermatological conditions. It consists of 10 items that assess the respondent's perception of the impact of their skin condition on various aspects of their quality of life during the past week, including symptoms and feelings related to dermatology, daily activities, leisure, work or school, personal relationships, and treatment. Each item is scored on a 4-point Likert scale (0 = "not at all relevant," 1 = "a little," 2 = "a lot," 3 = "very much"). The total score is the sum of the 10 items (0 to 30); a high score indicates poor quality of life. fr / ozLn / Lznz / E / Yii Product in research phase (IP-1) Ingredient Pharmaceutical product (mg / g) Vehicle (mg / g) Pharmaceutical substance the compound with formula (I) 20 - Excipients Liquid paraffin 100 100 Cetostearyl alcohol 72 72 Macrogol cetostearyl ether 18 18 Benzyl alcohol 10 10 Citric acid monohydrate 1 0.59 Sodium citrate 1 0.57 Disodium edetate 1.3 1.3 Hydrochloric acid 4.99 - Hydroxybutylanisole 0.2 0.2 Purified water up to 1 g up to 1 g Product in research phase (IP-2) fr / ozLn / Lznz / E / Yii Ingredient Pharmaceutical product (mg / g) Vehicle (mg / g) Pharmaceutical substance the compound with formula (I) 20 - Excipients Paraffin liquid 100 100 Cetostearyl alcohol 72 72 Macrogol cetostearyl ether 18 18 Benzyl alcohol 10 10 Citric acid monohydrate 1 0.59 Sodium citrate dihydrate - 0.57 Disodium edetate 0.6 0.6 Hydrochloric acid 3M 17.7 — Hydroxybutylanisole 0.2 0.2 Purified water up to 1 g up to 1 g CLAUSES

Claims

1. A compound with the general formula (I) 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3d]pyrimidin-4-yl)1,6-diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile, or a pharmaceutically acceptable salt thereof, for use in the treatment of cutaneous lupus erythematosus.

2. The compound to be used in accordance with clause 1, wherein the treatment is for discoid lupus erythematosus.

3. The compound to be used in accordance with clause 1 or 2, where the treatment is a topical treatment.

4. The compound to be used in accordance with any of the above clauses, wherein the compound with formula (I) or a pharmaceutically acceptable salt thereof is administered in a cream.

5. The compound to be used in accordance with any of the above clauses, wherein the compound with formula (I), or a pharmaceutically acceptable salt thereof, is administered at a concentration of 20 mg / g.

6. The compound to be used in accordance with any of the above clauses, wherein the compound with formula (I), or a pharmaceutically acceptable salt thereof, is administered as a twice-daily application.

7. A pharmaceutical composition for use in the treatment of cutaneous lupus erythematosus comprising a compound with the formula (I) fr / ozLn / ίζηζ / Β / γι 3-[ (3S,4R)-3-methyl-6-(7H-pyrrolo[2,3 d]pyrimidin-4-yl)1,6-diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile, or a pharmaceutically acceptable salt thereof, as an active ingredient.

8. The pharmaceutical composition to be used in accordance with clause 7, wherein the treatment is discoid lupus erythematosus.

9. The pharmaceutical composition to be used in the treatment in accordance with clause 7 or 8, where the pharmaceutical composition is topical.

10. The pharmaceutical composition to be used in the treatment in accordance with any of clauses 7 to 9, wherein the pharmaceutical composition is a cream.

11. The pharmaceutical composition for use in treatment according to any of clauses 7 to 10, wherein the compound with formula (I), or a pharmaceutically acceptable salt thereof, is administered at a concentration of 20 mg / g.

12. The pharmaceutical composition for use in treatment according to any of clauses 7 to 11, wherein the compound with formula (I), or a pharmaceutically acceptable salt thereof, is administered as a twice-daily application.

13. A method for use in the treatment of cutaneous lupus erythematosus in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of the compound with formula (I). fr / OZLÍV ί7Π7 / Β / ΥΙ 3-[ (3S,4R)-3-methyl-6-(7H-pyrrolo[2,3 d]pyrimidin-4-yl) 1,6-diazaspiro[3,4]octan-1-yl]-3-oxopropanenitrile, or a pharmaceutically acceptable salt thereof.

14. The method to be used in accordance with clause 13, where the treatment is for discoid lupus erythematosus.

15. The method to be used in treatment in accordance with clause 13 or 14, where administration is topical.

16. The method to be used in treatment in accordance with any of clauses 13 to 15 above, wherein the topical administration is a cream.

17. The method for use in treatment according to any of clauses 13 to 16 above, wherein the compound with formula (I), or a pharmaceutically acceptable salt thereof, is administered at a concentration of 20 mg / g.

18. A therapeutic or preventive agent for cutaneous lupus erythematosus, comprising a compound with the formula (I) fr / ozLn / Lznz / E / Yii 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3d]pyrimidin-4-yl)1,6-diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile, or a pharmaceutically acceptable salt thereof, as an active ingredient.

19. The therapeutic or preventive agent in accordance with clause 18 for the treatment or prevention of discoid lupus erythematosus.

20. The therapeutic or preventive agent in accordance with clause 18 or 19, wherein the therapeutic or preventive agent for discoid lupus erythematosus is a topical agent.

21. The therapeutic or preventive agent in accordance with any of clauses 18 to 20 above, wherein the therapeutic or preventive agent is a cream.

22. The therapeutic or preventive agent in accordance with any of clauses 18 to 21 above, wherein the compound with formula (I), or a pharmaceutically acceptable salt thereof, is administered at a concentration of 20 mg / g.

23. The therapeutic or preventive agent in accordance with any of clauses 18 to 22 above, wherein the compound with formula (I), or a pharmaceutically acceptable salt thereof, is administered as a twice-daily application.

24. A pharmaceutical formulation for topical administration comprising - the compound of formula (I) and, one or more of a pharmaceutically acceptable excipient selected from: - a base, such as liquid paraffin, surfactants, emulsifiers, stabilizers, such as cetostearyl alcohol and macrogol cetostearyl ether, pH regulators, buffers, such as phosphate or citrate salts and hydrochloric acid, - preservatives, - antioxidants, - chelating agents, - acidifying agents, and - purified water 25. The pharmaceutical formulation in accordance with clause 24, wherein the base is liquid paraffin, which is present in an amount of between approximately 50 mg / g and approximately 500 mg / g.

26. The pharmaceutical formulation in accordance with clause 25, wherein liquid paraffin is present in an amount of between approximately 75 mg / g and approximately 300 mg / g, and especially 100 mg / g.

27. The pharmaceutical formulation in accordance with any of clauses 24 to 26, wherein the surfactant, emulsifier, stabilizer are one or more of cetostearyl alcohol and macrogol cetostearyl ether.

28. The pharmaceutical formulation in accordance with clause 27, wherein cetostearyl alcohol is present in an amount of between approximately 20 mg / g and approximately 100 mg / g.

29. The pharmaceutical formulation in accordance with clause 28, wherein cetostearyl alcohol is present in an amount of between approximately 40 mg / g and approximately 80 mg / g, and especially 72 mg / g.

30. The pharmaceutical formulation in accordance with clause 27, wherein macrogol cetostearyl ether is present in an amount of between approximately 9 mg / g and approximately 25 mg / g.

31. The pharmaceutical formulation in accordance with clause 30, wherein macrogol cetostearyl ether is present in an amount of between approximately 15 mg / g and approximately 20 mg / g, and especially 18 mg / g.

32. The pharmaceutical formulation in accordance with any of clauses 24 to 31 above, wherein the buffer, pH regulator is selected from phosphate or citrate salts.

33. The pharmaceutical formulation in accordance with clause 32, wherein the buffer, pH regulator and citric acid monohydrate are present in an amount of between approximately 0.5 mg / g and approximately 4 mg / g.

34. The pharmaceutical formulation in accordance with clause 33, wherein citric acid monohydrate is present in an amount of between approximately 0.7 mg / g and approximately 2 mg / g, and especially 1 mg / g.

35. The pharmaceutical formulation in accordance with clause 32, wherein the buffer, the pH regulator is sodium citrate dihydrate, wherein there is an amount of between approximately 0 mg / g and approximately 1 fr / OZLÍV 17P7 / B / YI mg / g.

36. The pharmaceutical formulation in accordance with clause 35, wherein sodium citrate dihydrate is absent.

37. The pharmaceutical formulation in accordance with any of clauses 24 to 36, wherein the preservative is benzyl alcohol.

38. The pharmaceutical formulation in accordance with clause 37, wherein benzyl alcohol is present in an amount of between approximately 7 mg / g and approximately 13 mg / g.

39. The pharmaceutical formulation in accordance with clause 38, wherein benzyl alcohol is present in an amount of between approximately 9 mg / g and approximately 11 mg / g, and especially 10 mg / g.

40. The pharmaceutical formulation in accordance with any of clauses 24 to 39, wherein the antioxidant is butylhydroxyanisole.

41. The pharmaceutical formulation in accordance with clause 40, wherein hydroxybutylanisole is present in an amount of between approximately 0.05 mg / g and approximately 0.3 mg / g.

42. The pharmaceutical formulation in accordance with clause 41, wherein hydroxybutylanisole is present in an amount of between approximately 0.1 mg / g and approximately 0.25 mg / g, and especially 0.2 mg / g.

43. The pharmaceutical formulation in accordance with any of clauses 24 to 42, wherein the chelating agent is EDTA.

44. The pharmaceutical formulation in accordance with clause 43, wherein the chelating agent is disodium edetate.

45. The pharmaceutical formulation in accordance with clause 44, wherein disodium edetate is present in an amount of between approximately 0.05 mg / g and approximately 1.5 mg / g.

46. ​​The pharmaceutical formulation in accordance with clause 45, wherein disodium edetate is present in an amount of between approximately 0.5 mg / g and approximately 1 mg / g, and especially 0.6 mg / g.

47. The pharmaceutical formulation in accordance with any of clauses 24 to 46, wherein the acidifying agent is hydrochloric acid.

48. The pharmaceutical formulation in accordance with clause 47, wherein hydrochloric acid is present in an amount of between approximately 0 mg / g and approximately 25 mg / g.

49. The pharmaceutical formulation in accordance with clause 48, wherein hydrochloric acid is present in an amount of between approximately 10 mg / g and approximately 20 mg / g, and especially 17.7 mg / g.

50. The pharmaceutical formulation in accordance with any of clauses 24 to 49, wherein purified water is present in an amount of between approximately 500 mg / g and approximately 900 mg / g.

51. The pharmaceutical formulation in accordance with clause 50, wherein purified water is present in an amount of 760 mg / g.

52. The pharmaceutical formulation in accordance with any of clauses 24 to 51, wherein the compound with formula (I) is present in an amount of 1 mg / g, 3 mg / g, 8 mg / g or 20 mg / g.

53. The pharmaceutical formulation for topical administration comprising the compound with formula (I), 1 mg / g, liquid paraffin, 100 mg / g, cetostearyl alcohol, 72 mg / g, macrogol cetostearyl ether, 18 mg / g, benzyl alcohol, 10 mg / g, citric acid monohydrate, 0.78 mg / g, butylated hydroxyanisole, 0.2 mg / g, disodium edetate, 0.6 mg / g, sodium citrate dihydrate, 0.31 mg / g, and purified water, 797 mg / g.

54. The pharmaceutical formulation for topical administration comprising the compound with formula (I), 3 mg / g, liquid paraffin, 100 mg / g, cetostearyl alcohol, 72 mg / g, macrogol cetostearyl ether, 18 mg / g, benzyl alcohol, 10 mg / g, citric acid monohydrate, 1.0 mg / g, butylated hydroxyanisole, 0.2 mg / g, disodium edetate, 0.6 mg / g, 3M hydrochloric acid, 1.08 mg / g, and purified water, 794 mg / g.

55. The pharmaceutical formulation for topical administration comprising the compound with formula (I), 8 mg / g, liquid paraffin, 100 mg / g, cetostearyl alcohol, 72 mg / g, macrogol cetostearyl ether, 18 mg / g, benzyl alcohol, 10 mg / g, citric acid monohydrate, 1.0 mg / g, butylated hydroxyanisole, 0.2 mg / g, disodium edetate, 0.6 mg / g, 3M hydrochloric acid, 6.43 mg / g, and purified water, 784 mg / g.

56. The pharmaceutical formulation for topical administration comprising the compound with formula (I), 20 mg / g, liquid paraffin, 100 mg / g, cetostearyl alcohol, 72 mg / g, macrogol cetostearyl ether, 18 mg / g, benzyl alcohol, 10 mg / g, citric acid monohydrate, 1 mg / g, butylated hydroxyanisole, 0.2 mg / g, disodium edetate, 0.6 mg / g, 3M hydrochloric acid, 17.7 mg / g, and purified water, 760 mg / g.

57. The pharmaceutical formulation according to any of clauses 24 to 56, wherein the formulation is a cream. It is stated that, as of this date, the best method known to the applicant for carrying out the aforementioned invention is that which is clear from the present description of the invention. fr / OZLÍV ί7Π7 / Β / YI CLAIMS fr / ozLn / Lznz / E / Yi Having described the invention as above, the following claims are claimed as property:

1. A compound of the general formula (I) 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3d]pyrimidin-4-yl)1,6-diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile, or a pharmaceutically acceptable salt thereof, for use in the treatment of cutaneous lupus erythematosus.

2. The compound for use according to claim 1, wherein the treatment is for discoid lupus erythematosus. 3.The compound for use according to any of the preceding claims, wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, is administered in the form of a cream.

4. The compound for use according to any of the preceding claims, wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, is administered at a concentration of 20 mg / g.

5. A pharmaceutical composition for use in the treatment of cutaneous lupus erythematosus, comprising a compound of formula (I) fr / ozLn / Lznz / E / Yii 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3d]pyrimidin-4-yl)-1,6-diazaspiro[3,4]octan-l-yl]-3-oxopropanenitrile, or a pharmaceutically acceptable salt thereof, as an active ingredient.

6. The pharmaceutical composition for use according to claim 5, wherein the treatment is discoid lupus erythematosus. 7.The pharmaceutical composition for use in the treatment according to any one of claims 5 to 6, wherein the pharmaceutical composition is a cream.

8. The pharmaceutical composition for use in the treatment according to any one of claims 5 to 7, wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, is administered at a concentration of 20 mg / g.

9. A pharmaceutical formulation for topical administration, characterized in that it comprises - the compound of formula (I) and, one or more of a pharmaceutically acceptable excipient selected from: - a base, such as liquid paraffin, surfactants, emulsifiers, stabilizers, such as cetostearyl alcohol and macrogol cetostearyl ether, pH regulators, buffers, such as phosphate or citrate salts and hydrochloric acid, - preservatives, - antioxidants, - chelating agents, - acidifying agents, and - purified water. 10.The pharmaceutical formulation according to claim 9, characterized in that the base is liquid paraffin in an amount of between approximately 50 mg / g and approximately 500 mg / g.

11. The pharmaceutical formulation according to claim 9 or 10, characterized in that the cetostearyl alcohol is present in an amount of between approximately 20 mg / g and approximately 100 mg / g.

12. The pharmaceutical formulation according to any one of claims 9 to 11, characterized in that the macrogol cetostearyl ether is present in an amount of between approximately 9 mg / g and approximately 25 mg / g.

13. The pharmaceutical formulation according to any one of claims 9 to 12, characterized in that the phosphate or citrate salt is citric acid monohydrate in an amount of between approximately 0.5 mg / g and approximately 4 mg / g. 14.The pharmaceutical formulation according to any one of claims 9 to 12, characterized in that the phosphate or citrate salt is sodium citrate dihydrate in an amount of between 0 mg / g and approximately 1 mg / g.

15. The pharmaceutical formulation according to any one of claims 9 to 14, characterized in that the preservative is benzyl alcohol in an amount of between approximately 7 mg / g and approximately 13 mg / g.

16. The pharmaceutical formulation according to any one of claims 9 to 15, characterized in that the antioxidant is butylated hydroxyanisole in an amount of between approximately 0.05 mg / g and approximately 0.3 mg / g.

17. The pharmaceutical formulation according to any one of claims 9 to 16, characterized in that the chelating agent is disodium edetate in an amount of between approximately 0.05 mg / g and approximately 1.5 mg / g. fr / ozLn / Lznz / E / Yii 18.The pharmaceutical formulation according to any one of claims 9 to 17, characterized in that the acidifying agent is hydrochloric acid in an amount of between approximately 0 mg / g and approximately 25 mg / g.

19. The pharmaceutical formulation according to any one of claims 9 to 18, characterized in that purified water is present in an amount of between approximately 500 mg / g and approximately 900 mg / g.

20. The pharmaceutical formulation according to any one of claims 9 to 19, characterized in that the compound of formula (I) is present in an amount of 1 mg / g, 3 mg / g, 8 mg / g, or 20 mg / g. 21.The pharmaceutical formulation according to any of claims 9 to 20, characterized in that it comprises the compound with formula (I), 20 mg / g; liquid paraffin, 100 mg / g; cetostearyl alcohol, 72 mg / g; macrogol cetostearyl ether, 18 mg / g; benzyl alcohol, 10 mg / g; citric acid monohydrate, 1 mg / g; butylated hydroxyanisole, 0.2 mg / g; disodium edetate, 0.6 mg / g; 3 M hydrochloric acid, 17.7 mg / g; and purified water, 760 mg / g.