Il-13 antibodies for treatment of atopic dermatitis

Abstract

Provided herein are methods, uses, and pharmaceutical compositions of anti-IL-13 antibodies, such as Larizumab, for the treatment of atopic dermatitis in pediatric patients. Also provided herein are doses and dosing regimens for methods and uses of anti-IL-13 antibodies, such as Larizumab, for the treatment of atopic dermatitis in pediatric patients.

Description

Technical Field

[0001] The present invention relates to methods, uses and pharmaceutical compositions of anti-IL-13 antibodies such as lebrikizumab for treating atopic dermatitis in pediatric patients. The present invention also relates to dosages and administration regimens of methods and uses of anti-IL-13 antibodies such as lebrikizumab for treating atopic dermatitis in pediatric patients. Background Art

[0002] Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease characterized by erythema with exudation, dryness, lichenification and pruritus. It is one of the most common inflammatory skin diseases in developed countries, with a lifetime prevalence of 10% to 20% (Deckers et al., PLoS One 2012; 7: e39803; Weidinger et al., Lancet 2016; 387: 1109-22; Weidinger et al., Nature Reviews Disease Primers 2018; 4: 1). According to estimates from the International Study of Asthma and Allergies in Children (ISAAC), 15% to 20% of children and 1% to 3% of adults worldwide suffer from AD.

[0003] AD is more common in children than in adults and is often first diagnosed in children (Silverberg, Ann Allergy Asthma Immunol. 2019; 123 (2): 144-151). Most cases of AD begin before the age of 5 (85%) and tend to be associated with allergic sensitization (Bieber et al., N Engl J Med. 2008; 358: 1483-94; Kim et al., J Am Acad Dermatol. 2016; 75 (4): 681-687.e11; Silverberg and Duran-McKinster, Dermatol Clin. 2017; 35: 351-363). The prevalence of AD peaks in childhood (estimated at 14%), declines in adolescence (approximately 8%), and remains stable throughout adulthood (6% to 8%). AD is a chronic disease. Although AD can spontaneously resolve in young children, it is often the first manifestation of a condition that causes allergic rhinitis, asthma, and food allergies, often referred to as an atopic march (Illi, J Allergy Clin Immunol. 2004; 113:925-31; Spergel, Immunol Allergy Clin North Am 2010; 30:269-80; Davidson, J Allergy Clin Immunol. 2019 Jan 9. pii:S0091-6749(19)30014–4). Children with moderate to severe AD have approximately a 50% risk of developing asthma and a 75% risk of developing allergic rhinitis (Thomsen, ISRNAllergy 2014; 2014: 1-7).

[0004] Interleukin (IL) -13 is a key mediator of T-helper cell type 2 (Th2) inflammation, signaling through the heterodimeric receptor IL-4R / IL-13R1. Several lines of evidence suggest that IL-13 is a key pathogenic component in AD. In AD skin, increased IL-13 expression has been consistently reported (Tsoi L, et al. Journal of Investigative Dermatology. 2019; 139(7): 1480-1489; Bieber T. Allergy. 2020; 75(1): 54-62), and some reports suggest a relationship between IL-13 expression and disease severity (La Grutta S, et al., Allergy 60: 391-5, 2005). Increased IL-13 has also been reported in the serum of AD patients (Novak N, et al., J Invest Dermatol 2002; 119: 8705; WO2016149276), and some studies have reported an increase in IL-13-expressing T cells in the blood of AD patients (Akdis M, et al., J Immunol 1997; 159: 46119; Aleksza M, et al., Br J Dermatol 2002; 147: 113541; La Grutta S, et al., Allergy 2005; 60: 3915).

[0005] Treatment of AD mainly includes avoiding triggers, hydrating the skin during bathing, using moisturizers, and anti-inflammatory therapies such as topical corticosteroids (TCS). In many patients, treatment with TCS provides some symptom relief, but does not always adequately control the disease. For those with persistent moderate to severe disease and poor response to TCS, step-up options include topical calcineurin inhibitors (TCNI), phototherapy, and immunosuppressants such as oral corticosteroids, cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil. These drugs are not available to patients worldwide. Among them, cyclosporine is approved for the treatment of moderate to severe AD in many European countries, and its use is limited to patients aged 16 years and older (up to 8 weeks [NEORAL]). Cyclosporine is a potent immunosuppressant that can lead to increased susceptibility to infection and reduced cancer immune surveillance. Other commonly recognized toxicities of cyclosporine include hypertension and impaired renal and liver function.

[0006] For pediatric AD, systemic immunosuppressants are generally not recommended by current guidelines because they are associated with a significant risk of side effects (Chu, Clin Rev Allergy Immunol. 2021; 61(2): 114-127). In addition to well-known safety issues, low patient satisfaction with treatment is also common. Less than one-third of patients are satisfied with their current treatment regimen.

[0007] There remains an unmet medical need for safe and effective therapies and treatment regimens for moderate to severe AD in children. Summary of the invention

[0008] Provided herein are methods, uses, and pharmaceutical compositions of anti-IL-13 antibodies, such as lebrikizumab, for treating atopic dermatitis in pediatric patients. Also provided herein are dosages and dosing regimens for methods and uses of anti-IL-13 antibodies, such as lebrikizumab, for treating atopic dermatitis in pediatric patients.

[0009] In one aspect, there is provided herein a method for treating moderate to severe atopic dermatitis in a patient in need, and the method includes applying levitra to the patient, wherein the patient is 6 months to 12 years old, and the body weight is at least 6 kilograms (kg). In some embodiments, there is provided herein a method for treating moderate to severe atopic dermatitis, and the method includes: selecting a patient with moderate to severe atopic dermatitis, 6 months to 12 years old, and a body weight of at least 6kg, and applying levitra to the patient. In some embodiments, the patient is treated for a 16-week treatment period. During treatment, levitra is applied to the patient with a dosage and frequency selected based on the patient's weight. In some embodiments, when the patient has a body weight of 40kg or more, levitra is applied to the patient with 500mg in the 0th and 2nd weeks, and levitra is applied to the patient with 250mg every two weeks from the 4th week to the 14th week (e.g., in the 4th week, the 6th week, the 8th week, the 10th week, the 12th week, the 14th week). In some embodiments, when the patient has a body weight of 15 kg to less than 40 kg, levitra is administered to the patient at 250 mg at week 0, and levitra is administered to the patient at 250 mg once every four weeks from week 2 to week 14 (e.g., at week 2, week 6, week 10, week 14). In some embodiments, when the patient has a body weight of 6 kg to less than 15 kg, levitra is administered at 125 mg at week 0, and levitra is administered once every four weeks from week 2 to week 14 (e.g., at week 2, week 6, week 10, week 14).

[0010] In another aspect, there is provided herein a method for treating moderate to severe atopic dermatitis in a patient in need, and the method includes applying levitra to the patient, wherein the patient is 12 to 18 years old, and the body weight is less than 40kg. In some embodiments, there is provided herein a method for treating moderate to severe atopic dermatitis, and the method includes: selecting a patient with moderate to severe atopic dermatitis, 12 to 18 years old, and a body weight less than 40kg, and applying levitra to the patient. In some embodiments, the patient is treated for a 16-week treatment period. During treatment, levitra is applied to the patient with a dosage and frequency selected based on the patient's weight. In some embodiments, when the patient has a body weight of 15kg to less than 40kg, levitra is applied to the patient with 250mg at week 0, and levitra is applied to the patient with 250mg every four weeks from the 2nd week to the 14th week (e.g., at the 2nd week, the 6th week, the 10th week, the 14th week). In some embodiments, when the patient has a body weight of 6 kg to less than 15 kg, levitra is administered at 125 mg at week 0, and levitra is administered at 125 mg once every four weeks from week 2 to week 14 (e.g., at week 2, week 6, week 10, week 14).

[0011] In another aspect, provided herein is a method for treating moderate to severe atopic dermatitis, and the method comprises: selecting a patient with moderate to severe atopic dermatitis and weighing 6 kg to less than 15 kg, and administering levitra to the patient at 125 mg at week 0, and administering levitra to the patient at 125 mg once every four weeks from week 2 to week 14. In some embodiments, the patient is 6 months to 12 years old. In some embodiments, the patient is 12 to 18 years old.

[0012] In another aspect, provided herein is a method for treating moderate to severe atopic dermatitis, and the method comprises: selecting a patient with moderate to severe atopic dermatitis and weighing 15 kg to less than 40 kg, and administering levitra to the patient at 250 mg at week 0, and administering levitra to the patient at 250 mg once every four weeks from week 2 to week 14. In some embodiments, the patient is 6 months to 12 years old. In some embodiments, the patient is 12 to 18 years old.

[0013] In another aspect, provided herein is a method for treating moderate to severe atopic dermatitis, and the method comprises: selecting a patient with moderate to severe atopic dermatitis and weighing 40 kg or more, and administering levitra to the patient at 500 mg at weeks 0 and 2, and administering levitra to the patient at 250 mg once every two weeks from week 4 to week 14. In some embodiments, the patient is 6 months to 12 years old.

[0014] In some embodiments, the patient has an eczema area and severity index (EASI) score of 16 or more, an investigator global assessment (IGA) score of 3 or more, and more than 10% of the body surface area (BSA) is affected by atopic dermatitis before the administration of levitra. In some embodiments, the patient has an insufficient response to topical corticosteroids before the administration of levitra. In some embodiments, when the patient is 6 years old or older, the patient has atopic dermatitis for at least 12 months. In some embodiments, when the patient is 6 months to less than 6 years old, the patient has atopic dermatitis for at least 6 months.

[0015] In some embodiments, the method further comprises determining the EASI score of the patient after the treatment period (e.g., at week 16). In some embodiments, the EASI score determined after the treatment period (e.g., at week 16) is reduced by 75% or more compared to the EASI score determined before administration of levitra. In some embodiments, the EASI score determined after the treatment period (e.g., at week 16) is reduced by 90% or more compared to the EASI score determined before administration of levitra.

[0016] In some embodiments, the method further comprises determining the patient's IGA score after the treatment period (e.g., at week 16). In some embodiments, the IGA score determined after the treatment period (e.g., at week 16) is 0 or 1, and the IGA score determined after the treatment period (e.g., at week 16) is reduced by 2 points or more compared to the IGA score determined before administration of lebron jamesmab.

[0017] In some embodiments, the method further comprises determining the patient's pruritus numeric rating scale (NRS) score after the treatment period (e.g., at week 16). In some embodiments, the pruritus NRS score determined after the treatment period (e.g., at week 16) is reduced by 4 points or more compared to the pruritus NRS score determined before administration of lebrikizumab.

[0018] In some embodiments, the method further comprises determining one or more of the following characteristics of the patient at week 16: (i) percentage of BSA affected by atopic dermatitis; (ii) DLQI, cDLQI and / or IDLQI; (iii) PRISM; (iv) SCORAD; (v) PROMIS anxiety, PROMIS depression, PROMIS sleep disorder and / or PROMIS sleep-related impairment; (vi) POEM; (vii) EQ-5D-Y and / or EQ-5D-5L; (viii) mSQAAQ; (ix) DFI; (x) WPAI-AD-CG.

[0019] In some embodiments, kinizumab is administered subcutaneously to a patient. In some embodiments, kinizumab is administered to a patient using a subcutaneous administration device, such as a prefilled syringe, a disposable pen injection device, a microneedle device, a microinfusion device, a needle-free injection device, or an autoinjector device.

[0020] In another aspect, provided herein is levitra or a pharmaceutical composition comprising levitra for treating moderate to severe atopic dermatitis in patients aged 6 months to 12 years and weighing at least 6 kg. Also provided is the use of levitra in the preparation of a medicament for treating moderate to severe atopic dermatitis in patients aged 6 months to 12 years and weighing at least 6 kg.

[0021] In another aspect, provided herein is levitra or a pharmaceutical composition comprising levitra for treating moderate to severe atopic dermatitis in patients aged 12 to 18 years and weighing less than 40 kg. Also provided is the use of levitra in the preparation of a medicament for treating moderate to severe atopic dermatitis in patients aged 12 to 18 years and weighing less than 40 kg.

[0022] In another aspect, provided herein is a levitra monoclonal antibody or a pharmaceutical composition comprising levitra monoclonal antibody for treating moderate to severe atopic dermatitis in patients with a body weight of 6kg to less than 15kg. Also provided is the use of levitra monoclonal antibody in the preparation of a drug, which is used to treat moderate to severe atopic dermatitis in patients with a body weight of 6kg to less than 15kg. In some embodiments, levitra monoclonal antibody is applied to such patients, 125mg is applied in week 0, and 125mg is applied every four weeks from week 2 to week 14. In some embodiments, the patient age is 6 months to 12 years old. In some embodiments, the patient age is 12 to 18 years old.

[0023] In another aspect, provided herein is a levitra monoclonal antibody or a pharmaceutical composition comprising levitra monoclonal antibody for treating moderate to severe atopic dermatitis in patients with a body weight of 15kg to less than 40kg. Also provided is the use of levitra monoclonal antibody in the preparation of a drug, which is used to treat moderate to severe atopic dermatitis in patients with a body weight of 15kg to less than 40kg. In some embodiments, levitra monoclonal antibody is applied to such patients, 250mg is applied in week 0, and 250mg is applied once every four weeks from week 2 to week 14. In some embodiments, the patient age is 6 months to 12 years old. In some embodiments, the patient age is 12 to 18 years old.

[0024] In another aspect, provided herein is a levitra monoclonal antibody or a pharmaceutical composition comprising levitra monoclonal antibody for treating moderate to severe atopic dermatitis in patients weighing 40 kg or more. Also provided is the use of levitra monoclonal antibody in the preparation of a medicament for treating moderate to severe atopic dermatitis in patients weighing 40 kg or more. In some embodiments, levitra monoclonal antibody is administered to such patients, 500 mg is administered in Week 0 and Week 2, and 250 mg is administered every two weeks from Week 4 to Week 14. In some embodiments, the patient is 6 months to 12 years old.

[0025] In some embodiments, the methods, uses, and pharmaceutical compositions described herein further comprise administering one or more topical corticosteroids to the patient. In some embodiments, the topical corticosteroid is triamcinoloneacetonide, hydrocortisone, or a combination of triamcinoloneacetonide and hydrocortisone. In some embodiments, the topical corticosteroid is administered simultaneously with levitra. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 is a schematic diagram of the Phase 3 study design described in Example 1 (KGBI). Abbreviations: PTS = Participants; PK = Pharmacokinetics; TCS = Topical Corticosteroids; V = Visit; W = Week. Footnotes: a Post-treatment safety follow-up will begin at Week 26 (or approximately 12 weeks after the last dose of the study intervention); b Participants who complete the study will be eligible to join the long-term extension study. "Decision" in this schematic represents an interim PK and safety assessment that evaluates enrolling the first 30 participants from Cohort 1 before enrolling younger participants from Cohort 2.

[0027] Figure 2 is a schematic diagram of the Phase 3 study design described in Example 2 (KGBJ). Abbreviations: V = visit; W = week. Footnotes: a Post-treatment safety follow-up will begin at Week 62 (or approximately 12 weeks after the last dose of lebrikizumab). DETAILED DESCRIPTION

[0028] Provided herein are methods, uses, and pharmaceutical compositions of anti-IL-13 antibodies, such as lebrikizumab, for treating atopic dermatitis in pediatric patients. Also provided herein are dosages and dosing regimens of methods and uses of anti-IL-13 antibodies, such as lebrikizumab, for treating atopic dermatitis in pediatric patients.

[0029] In one aspect, there is provided herein a method for treating moderate to severe atopic dermatitis in a patient in need, and the method includes applying levitra to the patient, wherein the patient is 6 months to 12 years old, and the body weight is at least 6 kilograms (kg). In some embodiments, there is provided herein a method for treating moderate to severe atopic dermatitis, and the method includes: selecting a patient with moderate to severe atopic dermatitis, 6 months to 12 years old, and a body weight of at least 6kg, and applying levitra to the patient. In some embodiments, the patient is treated for a 16-week treatment period. During treatment, levitra is applied to the patient with a dosage and frequency selected based on the patient's weight. In some embodiments, when the patient has a body weight of 40kg or more, levitra is applied to the patient with 500mg in the 0th and 2nd weeks, and levitra is applied to the patient with 250mg every two weeks from the 4th week to the 14th week (e.g., in the 4th week, the 6th week, the 8th week, the 10th week, the 12th week, the 14th week). In some embodiments, when the patient has a body weight of 15 kg to less than 40 kg, levitra is administered to the patient at 250 mg at week 0, and levitra is administered to the patient at 250 mg once every four weeks from week 2 to week 14 (e.g., at week 2, week 6, week 10, week 14). In some embodiments, when the patient has a body weight of 6 kg to less than 15 kg, levitra is administered at 125 mg at week 0, and levitra is administered once every four weeks from week 2 to week 14 (e.g., at week 2, week 6, week 10, week 14).

[0030] In another aspect, there is provided herein a method for treating moderate to severe atopic dermatitis in a patient in need, and the method includes applying levitra to the patient, wherein the patient is 12 to 18 years old, and the body weight is less than 40kg. In some embodiments, there is provided herein a method for treating moderate to severe atopic dermatitis, and the method includes: selecting a patient with moderate to severe atopic dermatitis, 12 to 18 years old, and a body weight less than 40kg, and applying levitra to the patient. In some embodiments, the patient is treated for a 16-week treatment period. During treatment, levitra is applied to the patient with a dosage and frequency selected based on the patient's weight. In some embodiments, when the patient has a body weight of 15kg to less than 40kg, levitra is applied to the patient with 250mg at week 0, and levitra is applied to the patient with 250mg every four weeks from the 2nd week to the 14th week (e.g., at the 2nd week, the 6th week, the 10th week, the 14th week). In some embodiments, when the patient has a body weight of 6 kg to less than 15 kg, levitra is administered at 125 mg at week 0, and levitra is administered at 125 mg once every four weeks from week 2 to week 14 (e.g., at week 2, week 6, week 10, week 14).

[0031] In another aspect, provided herein is a method for treating moderate to severe atopic dermatitis, and the method comprises: selecting a patient with moderate to severe atopic dermatitis and weighing 6 kg to less than 15 kg, and administering levitra to the patient at 125 mg at week 0, and administering levitra to the patient at 125 mg once every four weeks from week 2 to week 14. In some embodiments, the patient is 6 months to 12 years old. In some embodiments, the patient is 12 to 18 years old.

[0032] In another aspect, provided herein is a method for treating moderate to severe atopic dermatitis, and the method comprises: selecting a patient with moderate to severe atopic dermatitis and weighing 15 kg to less than 40 kg, and administering levitra to the patient at 250 mg at week 0, and administering levitra to the patient at 250 mg once every four weeks from week 2 to week 14. In some embodiments, the patient is 6 months to 12 years old. In some embodiments, the patient is 12 to 18 years old.

[0033] In another aspect, provided herein is a method for treating moderate to severe atopic dermatitis, and the method comprises: selecting a patient with moderate to severe atopic dermatitis and weighing 40 kg or more, and administering levitra to the patient at 500 mg at weeks 0 and 2, and administering levitra to the patient at 250 mg once every two weeks from week 4 to week 14. In some embodiments, the patient is 6 months to 12 years old.

[0034] In some embodiments, the patient has an eczema area and severity index (EASI) score of 16 or more, an investigator global assessment (IGA) score of 3 or more, and more than 10% of the body surface area (BSA) is affected by atopic dermatitis before the administration of levitra. In some embodiments, the patient has an insufficient response to topical corticosteroids before the administration of levitra. In some embodiments, when the patient is 6 years old or older, the patient has atopic dermatitis for at least 12 months. In some embodiments, when the patient is 6 months to less than 6 years old, the patient has atopic dermatitis for at least 6 months.

[0035] In some embodiments, moderate to severe atopic dermatitis can be determined by the American Academy of Dermatology Atopic Dermatitis Diagnosis and Evaluation Criteria (Eichenfield et al., J Am Acad Dermatol. 2014; 70(2): 338-351). The basic features that must be present for the diagnosis of AD include pruritus and acute, subacute, or chronic eczema, which consists of a typical morphological and age-specific pattern, or a history of chronicity or relapses. Age-specific patterns include involvement of the face, neck, and extensor muscles in infants and children; current or previous flexural lesions in any age group; and sparing of the inguinal and axillary areas. Important features are seen in most cases that support the diagnosis of AD, including early age of onset, atopy (personal and / or family history, and / or IgE reactivity), and xerosis. Clinical associations that help suggest a diagnosis of AD but are too nonspecific to be used to confirm or detect AD for research and epidemiological studies include atypical vascular reactions such as facial pallor, white scratch sign and delayed blanch response, keratosis pilaris or pityriasis alba or hyperlinear palms or ichthyosis, ocular or periorbital changes, other local findings such as perioral or periauricular lesions, perifollicular exacerbations or lichenoid or prurigo lesions. The diagnosis of AD also depends on the exclusion of conditions such as scabies, seborrheic dermatitis, contact dermatitis (irritant or allergic), ichthyosis, cutaneous T-cell lymphoma, psoriasis, photosensitive skin diseases, immunodeficiency diseases or other causes of erythroderma.

[0036] The severity of atopic dermatitis can also be determined by the "Hanifin and Rajka criteria", as described in the Hanifin and Rajka diagnostic criteria described in Acta Derm Venereol (Stockh) 1980; Suppl 92:44-7; or the "Rajka and Langeland criteria", as described in Rajka G and Langeland T, Acta Derm Venereol (Stockh) 1989; 144 (Suppl): 134.

[0037] Levitra is an IgG4 monoclonal antibody that binds to human IL-13 with high affinity and blocks IL-13 signaling through the IL-4R / IL-13R1 heterodimeric receptor. The amino acid sequence of Levitra is provided in Table 1. Levitra comprises three heavy chain CDRs: HCDR1 of SEQ ID NO: 1, HCDR2 of SEQ ID NO: 2, HCDR3 of SEQ ID NO: 3, and three light chain CDR3s: LCDR1 of SEQ ID NO: 4, LCDR2 of SEQ ID NO: 5, LCDR3 of SEQ ID NO: 6. Levitra comprises a heavy chain variable region (VH) of SEQ ID NO: 7 and a light chain variable region (VL) of SEQ ID NO: 8. Levitra comprises a heavy chain (HC) of SEQ ID NO: 9 and a light chain (LC) of SEQ ID NO: 10. C-terminal shearing of IgG antibodies can occur when one or two C-terminal amino acids are removed from the heavy chain of an IgG antibody. For example, if a C-terminal lysine (K) is present, it can be truncated or clipped from the heavy chain. The penultimate glycine (G) can also be truncated or clipped from the heavy chain. The N-terminal amino acid of IgG can also be modified. For example, an N-terminal glutamine (Q) or glutamic acid (E) can spontaneously cyclize to pyroglutamic acid (pE). SEQ ID NO:9 reflects these potential modifications of the heavy chain of levitra.

[0038] Table 1. Levitra sequences

[0039] Levitra can be formulated into a pharmaceutical composition suitable for administration to a patient together with a suitable carrier or excipient. For example, Levitra can be formulated into a pharmaceutical composition, as described in WO 2013 / 066866. The pharmaceutical composition may include 125mg, 250mg or 500mg of Levitra. In some embodiments, the concentration of Levitra in the pharmaceutical composition is between 100mg / mL and 150mg / mL, such as 125mg / mL. The pharmaceutical composition may also include 5mM-40mM histidine acetate buffer, pH 5.4 to 6.0. In some embodiments, the pharmaceutical composition also includes a polyol (e.g., sugar) at a concentration of 100mM-200mM, and / or a surfactant (e.g., polysorbate 20) at a concentration of 0.01%-0.1%. In one embodiment, the pharmaceutical composition comprises 125 mg / mL levitra, 20 mM histidine acetate buffer (pH 5.7), 175 mM sucrose, and 0.03% polysorbate 20.

[0040] In some embodiments, the kinzolizumab is administered subcutaneously to the patient in the future. In some embodiments, the kinzolizumab is administered to the patient in the future using a subcutaneous administration device. The subcutaneous administration device can be selected from a prefilled syringe, a disposable pen injection device, a microneedle device, a microinfusion device, a needle-free injection device, or an automatic injector device. Various subcutaneous administration devices, including automatic injector devices, are known in the art and are commercially available. Exemplary devices include, but are not limited to, prefilled syringes (e.g., BD HYPAK from Becton Dickinson) and other similar devices. READYFILL TM and STERIFILL SCF TM ; CLEARSHOT from Baxter TM copolymer prefilled syringe; and Daikyo Seiko CRYSTAL available from West Pharmaceutical Services prefilled syringes); disposable pen injection devices, such as the BD Pen from Becton Dickinson; ultra-tip and microneedle devices (such as the INJECT-EASE TM and microinfusion device; and H-PATCH available from Valeritas TM ) and needle-free injection devices (such as those available from Bioject and and available from Medtronic and patch devices). In some embodiments, the subcutaneous administration device is an autoinjector device as described in WO 2008 / 112472, WO 2011 / 109205, WO 2014 / 062488, and / or WO 2016 / 089864.

[0041] In some embodiments, the patient is treated with Jinzhu monoclonal antibody for a treatment period of 12-68 weeks, for example, 12 weeks, 14 weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, 24 weeks, 26 weeks, 28 weeks, 30 weeks, 32 weeks, 34 weeks, 36 weeks, 38 weeks, 40 weeks, 42 weeks, 44 weeks, 46 weeks, 48 ​​weeks, 50 weeks, 52 weeks, 54 weeks, 56 weeks, 58 weeks, 60 weeks, 62 weeks, 64 weeks, 66 weeks, 68 weeks. In some embodiments, the patient is treated with Jinzhu monoclonal antibody for a treatment period of 16 weeks. In some embodiments, the patient is treated with Jinzhu monoclonal antibody for a treatment period of 52 weeks. In some embodiments, the patient is treated with Jinzhu monoclonal antibody for a treatment period of 68 weeks. In some embodiments, the patient is treated with Jinzhu monoclonal antibody for a treatment period of 16 weeks, followed by a maintenance period of 52 weeks.

[0042] In some embodiments, Jinzhu monoclonal antibody is administered to the patient with a loading dose of 250mg or 500mg in the future, and then administered to the patient with a subsequent dose of 125mg or 250mg in the remaining time of the treatment period. The loading dose can be applied to the patient several times (e.g., once or twice) at the beginning of treatment. After the loading dose, Jinzhu monoclonal antibody can be administered to the patient with a subsequent dose once every four weeks or once every two weeks. In some embodiments, Jinzhu monoclonal antibody is applied with a loading dose of 125mg in Week 0, and then Jinzhu monoclonal antibody is applied with a subsequent dose of 125mg every four weeks from Week 2 for the remaining treatment period. In some embodiments, Jinzhu monoclonal antibody is applied with a loading dose of 250mg in Week 0, and then Jinzhu monoclonal antibody is applied with a subsequent dose of 250mg every four weeks from Week 2 for the remaining treatment period. In some embodiments, levitra is administered as a loading dose of 500 mg at Weeks 0 and 2, followed by subsequent doses of 250 mg of levitra once every two weeks starting at Week 4 for the remainder of the treatment period.

[0043] In some embodiments, levitra is administered to the patient at a dose and frequency selected based on the patient's weight. In some embodiments, when the patient has a body weight of 6kg to less than 15kg, levitra is administered at 125mg in Week 0, and levitra is administered at 125mg once every four weeks starting from Week 2 for the remainder of the treatment period. In some embodiments, when the patient has a body weight of 15kg to less than 40kg, levitra is administered to the patient at 250mg in Week 0, and levitra is administered to the patient once every four weeks starting from Week 2 for the remainder of the treatment period. In some embodiments, when the patient has a body weight of 40kg or more, levitra is administered to the patient at 500mg in Week 0 and Week 2, and levitra is administered to the patient once every two weeks starting from Week 4 for the remainder of the treatment period.

[0044] In some embodiments, the treatment period is 16 weeks. In some embodiments, when the patient has a body weight of 6 kg to less than 15 kg, levitra is administered at 125 mg in week 0, and levitra is administered once every four weeks from week 2 to week 14 (e.g., at week 2, week 6, week 10, week 14) at 125 mg. In some embodiments, when the patient has a body weight of 15 kg to less than 40 kg, levitra is administered to the patient at 250 mg in week 0, and levitra is administered to the patient once every four weeks from week 2 to week 14 (e.g., at week 2, week 6, week 10, week 14) at 250 mg. In some embodiments, when the patient has a body weight of 40 kg or more, levitra is administered to the patient at 500 mg at weeks 0 and 2, and levitra is administered to the patient at 250 mg once every two weeks from week 4 to week 14 (e.g., at week 4, week 6, week 8, week 10, week 12, week 14).

[0045] During and after treatment, the patient can be assessed for one or more features of the Atopic Dermatitis Disease Severity Measure (ADDSM), which identifies certain signs, symptoms, characteristics, or parameters associated with atopic dermatitis and can be assessed quantitatively or qualitatively. Exemplary ADDSMs include, but are not limited to, the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Body Surface Area (BSA), Severity Score of Atopic Dermatitis (SCORAD), Pruritus Numerical Rating Scale (NRS), Parent-Reported Pruritus Severity Measure (PRISM), Dermatology Life Quality Index (DLQI) score or Child DLQI (cDLQI) or Infant DLQI (IDLQI), Modified Subcutaneous Administration Assessment Questionnaire (mSQAAQ), Patient-Reported Outcomes Measurement Information System (PROMIS), PROMIS Anxiety, PROMIS Depression, PROMIS Sleep Disorders, PROMIS Sleep-Related Impairment, Patient-Directed Eczema Measure (POEM), European Quality of Life-5 Dimensions-Youth Version (EQ-5D-Y), European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L), Family Impact of Dermatitis (DFI), and Work Productivity and Activity Impairment Questionnaire: Caregivers of Atopic Dermatitis (WPAI-AD-CG).

[0046] ADDSM can be measured at baseline (before administration of levitra) and at one or more time points after administration of levitra. For example, ADDSM can be measured at the end of week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12, week 13, week 14, week 15, week 16, or more after initial treatment with levitra. The difference between the ADDSM value at a specific time point after the start of treatment and the ADDSM value at baseline is used to assess whether ADDSM has improved (e.g., decreased).

[0047] The "Eczema Area and Severity Index" or "EASI" is a 20-item scale developed by researchers for adults and children that assesses 2 dimensions of AD: the extent of disease in 4 body regions (head / neck, trunk, upper extremities, and lower extremities) and 4 clinical symptoms (erythema, edema / papules, excoriations, and lichenification). The severity of clinical symptoms is assessed on a scale of 0 (none) to 3 (severe) (Hanifin et al., Exp Dermatol. 2001; 10: 11-18). The scores for each of the 4 body regions are added together. The percentage distribution of BSA for each body region is 10% for the head / neck, 20% for the upper extremities, 30% for the trunk, and 40% for the lower extremities. Each subtotal is multiplied by the BSA represented by that region. The multipliers for the regional scores are different to reflect the relative proportions of the body regions in young children. In addition, each body area is assigned an area score from 0 to 6, depending on the percentage of skin in that area affected by AD: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each body area score is multiplied by the area affected. The resulting EASI ranges from 0 to 72 points, with the higher the score, the more severe the AD. The recall period for this scale is the current time.

[0048] The “Investigator Global Assessment” or “IGA” is a single-item scale administered by the investigator to assess the severity of AD in participants (Simpson E et al., J Am Acad Dermatol. 2020;83(3):839-846). The IGA consists of a 5-point scale ranging from 0 (clean) to 4 (severe), and the score is selected using the descriptor that best describes the overall appearance of the lesion at a given time point (see Table 2). Table 2 Researcher's overall assessment

[0049] Body surface area (BSA) is an investigator-reported assessment that estimates the extent of disease or skin involvement of a participant's AD. BSA is expressed as a percentage of the total body mass and will be reported by body location. BSA is determined by the investigator using the rule that the palm of the participant's hand is approximately 1% BSA.

[0050] The Pruritus Numerical Rating Scale (NRS) is an 11-point scale administered by participants aged ≥6 years to rate the severity of their worst itch in the past 24 hours, with 0 representing "no itch" and 10 representing "worst itch imaginable". Participants record their assessments daily (Yosipovitch et al., Br J Dermatol. 2019; 181(4): 761-769). The Pruritus NRS measures itch, which is most familiar to AD participants. Therefore, the questions are designed for self-report. Where possible, participants should read and complete the questions alone. When necessary, caregivers (parents or others) can read the questions and response options aloud to the AD patient. However, it is important that the participant's choice of response to the question is entered directly into the question. Caregivers must not influence or question the responses given by the AD patient. The baseline mean score for the maximum itch intensity of the Pruritus NRS will be determined based on the daily scores for the 7 days before randomization. A minimum of 4 daily scores in 7 days are required to calculate the baseline mean score.

[0051] The Parent-Reported Itch Severity Measure or PRISM is a single-item scale administered by parents / caregivers to report the overall severity of their child's itch. Parents / caregivers report the overall severity of their child's itch based on their child's behavior observed over the past 24 hours. Response options range from "no itch," "mild," "moderate," "severe," and "very severe." For participants younger than 6 years of age, the PRISM is completed by the parent / caregiver. A minimum of 4 daily response scores over 7 days is required to calculate a baseline mean response score.

[0052] The “Severity Scoring of Atopic Dermatitis” or “SCORAD” index is a 9-item assessment administered by the investigator and the participant that assesses three areas: (i) the investigator assesses the extent of AD (1 item), reported as a percentage of each defined body area and as the sum of all areas (maximum score of 100%); (ii) the investigator assesses the severity (intensity) of 6 specific symptoms of AD: erythema, edema / papules, exudation / crusting, excoriation, lichenification, and dryness (6 items) using a 4-point scale (i.e., none = 0, mild = 1, moderate = 2, severe = 3), with a maximum total score of 18 points; and (iii) the participant assesses subjective symptoms of pruritus and insomnia (2 items) using a 10-cm visual analog scale. Symptoms (pruritus and insomnia) were recorded by the participant or caregiver on a visual analog scale, where 0 indicates no symptoms and 10 indicates the most severe symptoms, with a maximum score of 20 points. For participants younger than 8 years, SCORAD was completed by the caregiver. The SCORAD index formula is: A / 5+7B / 2+C. In this formula, A is defined as degree (0-100), B is defined as severity (0-18), and C is defined as subjective symptoms (0-20). The maximum possible SCORAD score calculated based on the above three aspects is 103. The higher the score, the worse or more severe the condition (Stalder and Dermatology. 1993;186(1):23-31; Oranje et al., Br J Dermatol. 2007;157(4):645-648; Schram et al., Allergy. 2012;67(1):99-106). The recall period for degree and intensity was the current time, and the recall period for subjective symptoms of AD was the average of the past 3 days / nights.

[0053] The Dermatology Life Quality Index (DLQI) is a participant-administered, 10-item, validated adult quality of life (QoL) questionnaire covering 6 domains including symptoms and feelings, usual activities, leisure, work and school, relationships, and treatment. The recall period for this scale is during the “last week.” Response categories include “not at all,” “a little,” “a lot,” and “very much,” corresponding to 0, 1, 2, and 3 points, respectively, and a score of 0 for a non-answer (or “not relevant”) response. Scores range from 0 to 30, with higher scores indicating more severe impairment of QoL. A DLQI total score of 0 to 1 is considered to have no effect on the participant's health-related QoL (Hongbo et al., J Invest Dermatol. 2005; 125(4): 659-664), and a change of 4 points from baseline is considered the minimum clinically important difference threshold (Khilji et al., 2002, Br J Dermatol. 2002; 147(suppl 62): 25-54; Basra et al., Dermatology. 2015; 230(1): 27-33). The recall period for the DLQI is the past week. Participants aged 4 to <17 years will complete the children's DLQI (cDLQI) questionnaire and should continue to complete the cDLQI during the study (Lewis-Jones MS, Finlay AY. Br J Dermatol. 1995; 132: 942-949). For children younger than 4 years (i.e. up to 3 years 11 months), caregivers will complete the Infant DLQI (IDQOL) questionnaire and should continue to complete the IDQOL during the study (Lewis-Jones et al., Br J Dermatol. 2001; 144(1): 104-110; Basra et al., Br J Dermatol. 2013; 169(4): 760-768).

[0054] The modified subcutaneous administration assessment questionnaire (mSQAAQ) uses 10 questions to assess ease of use and confidence, e.g., acceptability and tolerability of using the device to administer subcutaneous injections of the study product. The participant's parent / caregiver will answer 10 questionnaire items about the characteristics of using the administration device using a 7-point Likert scale (from "strongly disagree" to "strongly agree") shortly after completing the injection. The characteristics assessed include ease of learning how to use the device, ease of use, ease of storage of the device, confidence in the ability to use the device, and confidence in the completion of the injection (Callis Duffin et al. 2016). Parents / caregivers complete the questionnaire on paper.

[0055] PROMIS (Patient Reported Outcomes Measurement Information System) is a set of person-centered measures that assess and monitor the physical, mental, and social health of adults and children (PROMIS WWW). PROMIS measures include the Anxiety and Depression Short Form, which assesses participants' symptoms over the past week. It can be used in the general population and in individuals with chronic illnesses.

[0056] The PROMIS Anxiety measure assesses the following items: self-reported fear (fear, panic), anxiety distress (worry, fear), hypervigilance (nervousness, jitteriness, restlessness), and physical symptoms related to arousal (racing heart, dizziness) (PROMIS Anxiety 2019, available at https: / / www.healthmeasures.net / images / PROMIS / manuals / PROMIS_Anxiety_Scoring_Manual.pdf). The PROMIS Anxiety Short Form (8 questions, 8a v2.0) is available in the Pediatric Self-Report (ages 8 to <18 years) and can be used by parents / caregivers as proxy reporters for their children (adolescents ≥5 years). Children younger than 5 years do not need to complete this assessment. Both the Pediatric Self-Report and Proxy-Report versions assess anxiety “in the past 7 days.” Response options range from 1 = never; 2 = rarely; 3 = sometimes; 4 = often; to 5 = almost always. Total raw scores are converted to T scores, with higher scores indicating more severe anxiety.

[0057] The PROMIS Depression Measure assesses the following items: self-reported negative emotions (sadness, guilt), self-view (self-criticism, feelings of worthlessness), social cognition (loneliness, interpersonal detachment), and decreased positive emotions and engagement (loss of interest, meaning, and purpose) (PROMISDepression 2019, available at https: / / www.healthmeasures.net / images / PROMIS / manuals / PROMIS_Depression_Sco ring_Manual.pdf). The PROMIS Depression Short Form (8av2.0 and 6a v2.0) is available in pediatric self-report (ages 8 to <18 years) and can be used by parents / caregivers as proxy reporters for their children (adolescents 5 years or older). Children younger than 5 years do not need to complete this assessment. Both the pediatric self-report and proxy report versions assess depression “in the past 7 days.” Response options range from 1 = never; 2 = rarely; 3 = sometimes; 4 = often; to 5 = almost always. Total raw scores are converted to T scores, with higher scores indicating more severe depression.

[0058] The PROMIS Sleep Disturbance tool assesses self-reported perceptions of sleep quality, sleep depth, and sleep-related restorativeness. This includes difficulties and concerns about falling asleep or staying asleep, as well as perceptions of sleep adequacy and satisfaction. The Sleep Disturbance Short Form is generic and not disease-specific. It assesses sleep disturbances in the past 7 days. This measure will be administered where a translation is available. The PROMIS Pediatric Short Form – Sleep Disturbance (8 questions, 8a v1) is available in Pediatric Self-Report (ages 8 to <18 years) and can be used by parents / caregivers as proxy reporters for their children (adolescents 5 years or older). Children younger than 5 years do not need to complete this assessment. Both the Pediatric Self-Report and Proxy Report versions assess anxiety “in the past 7 days.” Response options range from 1 = never; 2 = rarely; 3 = sometimes; 4 = often; to 5 = almost always. Total raw scores are converted to T scores, with higher scores indicating greater anxiety (Yu L et al., Behav Sleep Med. 2011;10(1):6-24).

[0059] The PROMIS Sleep-Related Impairment item bank focuses on self-reported perceptions of alertness, sleepiness, and fatigue during usual waking hours, and perceived functional impairment during waking hours associated with sleep problems or impaired alertness. Sleep-Related Impairment measures waking alertness, sleepiness, and function in the context of overall sleep-wake function. The Sleep-Related Impairment Short Form is generic and not disease-specific. It assesses sleep-related impairment in the past 7 days. This measure will be administered where a translation is available. The PROMIS Pediatric Short Form – Sleep-Related Impairment (8 questions, 8a v1) is available in Pediatric Self-Report (ages 8 to <18 years) and can be used by parents / caregivers as proxy reporters for their children (adolescents 5 years or older). Children younger than 5 years do not need to complete this assessment. Both the Pediatric Self-Report and Proxy Report versions assess anxiety “in the past 7 days.” Response options range from 1 = never; 2 = rarely; 3 = sometimes; 4 = often; to 5 = almost always. The total raw score was converted to a T score, with higher scores indicating higher levels of anxiety (Yu L et al., Behav Sleep Med. 2011; 10(1): 6-24).

[0060] The European Quality of Life-5 Dimensions-Young Version (EQ-5D-Y) is a widely used, general questionnaire that assesses health status "today" (EuroQol group). The EQ-5D-Y is self-completed for pediatric participants aged 8 years and older, and for children aged 4 to <8 years by parents / caregivers (proxy). Children younger than 4 years do not need to complete this assessment, as recommended by the developers. The questionnaire consists of two parts. The first part assesses 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression, with 3 possible response levels (no problems, some problems, or a lot of problems). This part of the EQ-5D-Y can be used to generate a health status index score, which is often used to calculate quality-adjusted life years for health economic analysis. The health status index score is calculated from the responses to the 3 dimensions, giving a single value on a scale ranging from less than 0 (where zero indicates a health status equivalent to death; negative values ​​indicate worse than death) to 1 (perfect health), with higher scores indicating better health utility. The second part of the questionnaire consisted of a visual analogue scale on which participants rated their perceived health status, ranging from 0 ("the worst health you can imagine") to 100 ("the best health you can imagine"). Research published by members of the EuroQol group showed evidence of the feasibility, reliability, and validity of this tool (Ravens-Sieberer et al., Qual Life Res. 2010; 19(6):887-897).

[0061] The European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L, EuroQol Research Foundation) is a standardized 5-item self-assessment tool for measuring health outcomes. It provides a simple descriptive profile and a single index value of health status and can be used for clinical and economic evaluation of health care and population health surveys. The European Quality of Life-5 Dimensions-5 Levels assesses 5 dimensions of health: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. The 5L version divides each dimension into 5 levels: no problems, slight problems, moderate problems, severe problems, and unable to perform / extreme problems. A total of 3125 health states are possible. In addition to the health profile, a single health state index value can be derived based on a formula that attaches weights to each level in each dimension. The index value ranges from less than 0 (where 0 represents a health state equivalent to death; negative values ​​represent worse than death) to 1 (perfect health). In addition, the EQ visual analog scale records the respondent's self-rated health status on a visual analog scale with a vertical scale (0 to 100). Participants rated their perceived health from 0 (worst health) to 100 (best health). Combined with health status data, it provides a comprehensive picture of the health status of the respondents.

[0062] The Patient Oriented Eczema Measure (POEM) is a 7-item scale administered by caregivers to assess disease severity in children and adults. Participants respond to questions about the frequency of 7 symptoms (itching, sleep disturbance, bleeding, weeping / oozing, cracking, flaking, and dryness / roughness) in the past week. Response categories include "none," "1 to 2 days," "3 to 4 days," "5 to 6 days," and "every day," with corresponding scores of 0, 1, 2, 3, and 4, respectively. Scores range from 0 to 28, with higher total scores indicating more severe disease (Charman et al., Arch Dermatol. 2004; 140(12): 1513-1519). High scores indicate poor quality of life. Caregivers should complete all POEM assessments even if participants reach adult age during the study.

[0063] The Dermatitis Family Impact (DFI) questionnaire is a 10-question, validated quality of life questionnaire administered by caregivers to assess the impact of AD on the quality of life of parents and family members of children with AD (Lawson et al., Br J Dermatol. 1998; 138(1): 107-113; Dodington et al., Br J Dermatol. 2013; 169(1): 31-46). The recall period is the entire "last week". Response options include "not at all", "a little", "a lot" and "very", corresponding to scores of 0, 1, 2 and 3, respectively. Scores range from 0 to 30, with higher scores indicating more severe QoL impairment. Caregivers should complete all Dermatitis Family Impact Assessments even if participants reach adulthood during the study period.

[0064] Work Productivity and Impaired Activity Questionnaire: Atopic Dermatitis Caregiver (WPAI-AD-CG) assesses the impact of participants' AD on the work productivity of parents / caregivers in the past 7 days. The WPAI-AD-CG contains 6 items divided into four areas: absence (absenteeism during work hours), attendance (impaired work / reduced work efficiency), work productivity loss (overall work impairment / absenteeism plus attendance), and impaired activity. Scores are calculated as percentage of impairment (Reilly et al., Pharmacoeconomics. 1993; 4 (5): 353-365), and the higher the score, the greater the impairment and the lower the productivity. Even if the participant reaches adult age during the study, the caregiver should complete all assessments of the WPAI-AD-CG.

[0065] In some embodiments, the patient's EASI score is determined after the treatment period (e.g., week 16). In some embodiments, the patient's EASI score determined after the treatment period (e.g., at week 16) is reduced by 50% or more compared to the EASI score determined before the administration of levitra, which means that the patient has reached "EASI 50". In some embodiments, the patient's EASI score determined after the treatment period (e.g., at week 16) is reduced by 75% or more compared to the EASI score determined before the administration of levitra, which means that the patient has reached "EASI 75". In some embodiments, the patient's EASI score determined after the treatment period (e.g., at week 16) is reduced by 90% or more compared to the EASI score determined before the administration of levitra, which means that the patient has reached "EASI 90".

[0066] In some embodiments, the patient's IGA score is determined after the treatment period (e.g., at week 16). In some embodiments, after the treatment period (e.g., at week 16), the patient's IGA score determined is 0 or 1, and the IGA score determined after the treatment period (e.g., at week 16) is reduced by 2 points or more compared to the IGA score determined before administration of levitra.

[0067] In some embodiments, the patient's pruritus NRS score is determined after the treatment period (e.g., at week 16). In some embodiments, the pruritus NRS score determined after the treatment period (e.g., at week 16) is reduced by 4 points or more compared to the patient's pruritus NRS score determined before administration of lebrikizumab.

[0068] In some embodiments, one or more of the following characteristics of the patient are determined after the treatment period (e.g., at week 16): (i) percentage of BSA affected by atopic dermatitis; (ii) DLQI, cDLQI and / or IDLQI; (iii) PRISM; (iv) SCORAD; (v) PROMIS anxiety, PROMIS depression, PROMIS sleep disorder and / or PROMIS sleep-related impairment; (vi) POEM; (vii) EQ-5D-Y and / or EQ-5D-5L; (viii) mSQAAQ; (ix) DFI; (x) WPAI-AD-CG.

[0069] In another aspect, provided herein is levitra or a pharmaceutical composition comprising levitra for treating moderate to severe atopic dermatitis in patients aged 6 months to 12 years and weighing at least 6 kg. Also provided is the use of levitra in the preparation of a medicament for treating moderate to severe atopic dermatitis in patients aged 6 months to 12 years and weighing at least 6 kg.

[0070] In another aspect, provided herein is levitra or a pharmaceutical composition comprising levitra for treating moderate to severe atopic dermatitis in patients aged 12 to 18 years and weighing less than 40 kg. Also provided is the use of levitra in the preparation of a medicament for treating moderate to severe atopic dermatitis in patients aged 12 to 18 years and weighing less than 40 kg.

[0071] In another aspect, provided herein is a levitra monoclonal antibody or a pharmaceutical composition comprising levitra monoclonal antibody for treating moderate to severe atopic dermatitis in patients with a body weight of 6kg to less than 15kg. Also provided is the use of levitra monoclonal antibody in the preparation of a drug, which is used to treat moderate to severe atopic dermatitis in patients with a body weight of 6kg to less than 15kg. In some embodiments, levitra monoclonal antibody is applied to such patients, 125mg is applied in week 0, and 125mg is applied every four weeks from week 2 to week 14. In some embodiments, the patient age is 6 months to 12 years old. In some embodiments, the patient age is 12 to 18 years old.

[0072] In another aspect, provided herein is a levitra monoclonal antibody or a pharmaceutical composition comprising levitra monoclonal antibody for treating moderate to severe atopic dermatitis in patients with a body weight of 15kg to less than 40kg. Also provided is the use of levitra monoclonal antibody in the preparation of a drug, which is used to treat moderate to severe atopic dermatitis in patients with a body weight of 15kg to less than 40kg. In some embodiments, levitra monoclonal antibody is applied to such patients, 250mg is applied in week 0, and 250mg is applied once every four weeks from week 2 to week 14. In some embodiments, the patient age is 6 months to 12 years old. In some embodiments, the patient age is 12 to 18 years old.

[0073] In another aspect, provided herein is a levitra monoclonal antibody or a pharmaceutical composition comprising levitra monoclonal antibody for treating moderate to severe atopic dermatitis in patients weighing 40 kg or more. Also provided is the use of levitra monoclonal antibody in the preparation of a medicament for treating moderate to severe atopic dermatitis in patients weighing 40 kg or more. In some embodiments, levitra monoclonal antibody is administered to such patients, 500 mg is administered in Week 0 and Week 2, and 250 mg is administered every two weeks from Week 4 to Week 14. In some embodiments, the patient is 6 months to 12 years old.

[0074] In some embodiments, the methods, purposes and pharmaceutical compositions described herein also include applying one or more topical corticosteroids (TCS) to the patient. Exemplary topical corticosteroids include but are not limited to triamcinolone acetonide, hydrocortisone and the combination of triamcinolone acetonide and hydrocortisone. Triamcinolone acetonide is usually formulated in an emulsifiable paste at a concentration of 0.1%, and hydrocortisone is usually formulated in an emulsifiable paste at a concentration of 1% or 2.5%. Some topical corticosteroids are considered to be highly efficient, such as betamethasone dipropionate, clobetasol propionate, diflorasone diacetate, fluocinonide and halobetasol propionate. Some topical corticosteroids are considered high potency, such as amcinonide, desoximetasone, halcinonide, and riamcinolone acetonide. Some topical corticosteroids are considered intermediate potency, such as betamethasone valerate, clocortolone pivalate, fluocinolone acetonide, flurandrenolide, fluocinonide, fluticasone propionate, hydrocortisone butyrate, hydrocortisone valerate, mometasone furoate, and prednicarbate. Some local corticosteroids are considered to be inefficient, such as alclometasone dipropionate, desonide and hydrocortisone. TCS can be applied to the affected area once a day, twice a day, three times a day or as needed. The use of TCS can be recorded in a diary. In some embodiments, before using levitra, the patient's topical application of corticosteroids is not adequately controlled. In some embodiments, the local corticosteroid is triamcinolone acetonide, hydrocortisone or a combination of triamcinolone acetonide and hydrocortisone. In some embodiments, the local corticosteroid is used simultaneously or sequentially with levitra.In some embodiments, the topical corticosteroid is administered concurrently with lebrikizumab.

[0075] As used herein, the terms "a", "an", "the" and similar terms used in the context of the disclosure (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

[0076] As used herein, the term "about" means within a reasonable vicinity of a stated value, for example, plus or minus 10% of the stated value.

[0077] As used herein, the term "antibody" refers to an immunoglobulin molecule that binds to an antigen. Embodiments of antibodies include monoclonal antibodies, polyclonal antibodies, human antibodies, humanized antibodies, chimeric antibodies, or conjugated antibodies. The antibody can be of any class (e.g., IgG, IgE, IgM, IgD, IgA) and any subclass (e.g., IgG1, IgG2, IgG3, IgG4).

[0078] An exemplary antibody is an immunoglobulin G (IgG) type antibody consisting of four polypeptide chains: two heavy chains (HC) and two light chains (LC), which are cross-linked by interchain disulfide bonds. The amino terminal portion of each of the four polypeptide chains includes a variable region of about 100-125 or more amino acids, which is primarily responsible for antigen recognition. The carboxyl terminal portion of each of the four polypeptide chains contains a constant region primarily responsible for effector function. Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region. Each light chain consists of a light chain variable region (VL) and a light chain constant region. IgG isotypes can be further divided into subclasses (e.g., IgG1, IgG2, IgG3, and IgG4).

[0079] The VH and VL regions can be further subdivided into highly variable regions, called complementarity determining regions (CDRs), interspersed with more conserved regions, called framework regions (FRs). CDRs are exposed on the surface of the protein and are important regions for the antigen binding specificity of antibodies. Each VH and VL consists of three CDRs and four FRs, arranged in the following order from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. Here, the three CDRs of the heavy chain are referred to as "HCDR1, HCDR2, and HCDR3," while the three CDRs of the light chain are referred to as "LCDR1, LCDR2, and LCDR3." CDRs contain most of the residues that form specific interactions with antigens. Amino acid residues can be assigned to CDRs according to well-known schemes, including Kabat (Kabat et al., "Sequences of Proteins of Immunological Interest," National Institutes of Health, Bethesda, Md. (1991)), Chothia (Chothia et al., "Canonical structures for the hypervariable regions of immunoglobulins", Journal of Molecular Biology, 196, 901-917 (1987); Al-Lazikani et al., "Standard conformations for the canonical structures of immunoglobulins", Journal of Molecular Biology, 273, 927-948 (1997)), North (North et al., "A New Clustering of Antibody CDR Loop Conformations", Journal of Molecular Biology, 273, 927-948 (1997)), and North (North et al., "A New Clustering of Antibody CDR Loop Conformations", Journal of Molecular Biology, 273, 927-948 (1997)). Biology, 406, 228-256 (2011)) or IMGT (the international ImMunoGeneTics database is available at www.imgt.org; see Lefranc et al., Nucleic Acids Res. 1999; 27: 209-212).

[0080] As used herein, unless otherwise indicated, the terms "bind" or "binds" refer to the ability of a protein or molecule to form a chemical bond or attractive interaction with another protein or molecule, which brings the two proteins or molecules into proximity as determined by common methods known in the art.

[0081] As used herein, the term "flare" refers to an increase in signs and / or symptoms that leads to an escalation of treatment, which may be an increase in dosage, a switch to a more potent type of medication, or the initiation of another medication.

[0082] The term "human IL-13" refers to human interleukin 13 (also known as P600), an immunomodulatory cytokine produced primarily by activated Th2 cells. There are two known human IL-13 isoforms: isoform a and isoform b. The term "human IL-13" as used herein refers collectively to all human IL-13 isoforms. The amino acid sequence of human IL-13 isoform a can be found at NCBI Accession No. NP_002179.2. The amino acid sequence of human IL-13 isoform b can be found at NCBI Accession No. NP_001341922.1.

[0083] As used herein, the term "inadequate response" refers to the failure to achieve good disease control of atopic dermatitis (e.g., failure to achieve IGA ≤ 2 or EASI 75) after treatment for the duration recommended by the product prescribing information, or the occurrence of a flare of atopic dermatitis while on treatment.

[0084] As used herein, the term "intolerance" refers to unacceptable toxicity (e.g., increased creatinine, elevated liver function test results, uncontrolled hypertension, loss of lower body sensation, headache, nausea, hirsutism) or the need for a drug at a dose or duration exceeding that specified in the prescribing information.

[0085] As used herein, the term "patient" refers to a human patient.

[0086] The term "topical corticosteroid" or "TCS" used herein includes Class I, Class II, Class III and Class IV topical corticosteroids. According to the Anatomical Therapeutic Chemistry (ATC) classification system of the World Health Organization, corticosteroids are classified as weak (Class I), medium (Class II) and effective (Class III) and very effective (Class IV) based on their activity compared with hydrocortisone. The effectiveness of Class IV TCS (very effective) is 600 times that of hydrocortisone, including clobetasol propionate and halcinonide. The effectiveness of Class III TCS (effective) is 50 to 100 times that of hydrocortisone, including but not limited to betamethasone valerate, betamethasone propionate, diflucortolone valerate, hydrocortisone-17-butyrate (hydrocortisone-17-butyrate), mometasone furoate and methylprednisolone aceponate (methylprednisolone aceponate). Class II TCS (moderate potency) are 2 to 25 times more potent than hydrocortisone and include, but are not limited to, clobetasone butyrate and triamcinolone acetonide. Class I TCS (weak or mild) include hydrocortisone, prednisolone, and methylprednisolone.

[0087] As used herein, "treatment" or "treating" refers to all processes in which the progression of the conditions or diseases disclosed herein can be slowed, controlled, delayed or stopped, or the symptoms of the conditions or diseases can be improved, but does not necessarily mean the complete elimination of all conditions or disease symptoms. Treatment includes the administration of proteins or nucleic acids or vectors or compositions to treat a disease or condition in a patient, particularly a human. Example Example 1. A randomized, double-blind, placebo-controlled Phase 3 study to evaluate the efficacy, safety, and pharmacokinetics of levitra compared with placebo in participants aged 6 months to <18 years with moderate to severe atopic dermatitis (KGBI).

[0088] This is a randomized, double-blind, placebo-controlled, phase 3 study to evaluate the efficacy, safety, and pharmacokinetics of levitra in participants aged 6 months to <18 years with moderate to severe AD. Figure 1 Participants were divided into 2 groups. Group 1 participants were 6 years to <18 years old, including 12 years to <18 years old with a weight of <40 kg, and 6 years to <12 years old (whose weight could be ≥40 kg). Group 2 participants were 6 months to <6 years old, including 2 years to <6 years old, and 6 months to <2 years old.

[0089] Study enrollment is staggered by age. Older participants in Cohort 1 are enrolled into the study first. An interim analysis will evaluate PK and safety parameters in the first 30 participants in Cohort 1 who complete Week 16 (or terminate early) before enrolling younger participants in Cohort 2.

[0090] Goals and End Points:

[0091] This study evaluated the following primary, secondary, and exploratory objectives and endpoints. Statistical analyses were performed for the primary endpoint and key secondary endpoints. Table 3. KGBI goals and endpoints

[0092] Study Design:

[0093] The study has four treatment periods: Study Periods I to IV. During Study Period I, appropriate informed consent and assent forms are signed prior to any study procedures. Investigators will review symptoms, risk factors, medical history, vaccination history, concomitant medications, and other inclusion and exclusion criteria to confirm eligibility. During Study Period II, standardized TCS treatment is initiated for all participants and continued until the end of the study.

[0094] Study Period III was a double-blind treatment period during which eligible participants were randomized in a 2: 1 ratio to receive either levitra or placebo. The levitra dose was selected based on the participant's weight (see Table 4). Table 4. Levitra dose based on participant weight.

[0095] Study Phase IV is the post-treatment safety follow-up phase. For participants who terminate the study early or complete the 16-week study but do not participate in the long-term extension study, safety follow-up assessments will be conducted 12 weeks after the last dose for final clinical and safety assessments. Participants who complete the 16-week study without the need for systemic rescue medication are eligible to participate in the long-term extension study, which aims to evaluate the long-term safety of lebrikizumab.

[0096] Patient population:

[0097] Approximately 300 participants were enrolled and randomized in a 2:1 ratio to receive levitra or placebo (200 participants:100 participants).

[0098] Inclusion Criteria: To be eligible in this trial, patients must meet all of the following criteria: 1. Age and weight requirements: (1) ≥6 months to <12 years old, weighing at least 6 kg, or (2) ≥12 years to <18 years old, weighing <40 kg. 2. Diagnosed with AD prior to screening, as described by the American Academy of Dermatology (Eichenfield et al., J Am Acad Dermatol. 2014; 70(2): 338-351), at least (1) 12 months if the participant was ≥ 6 years old, or (2) 6 months if the participant was 6 months to < 6 years old. 3. EASI score ≥16 at screening and baseline visits. 4. IGA score ≥ 3 (on a scale of 0 [clean] to 4 [severe]) at screening and baseline visits. 5. AD lesions in body surface area (BSA) ≥ 10% at screening and baseline visits. 6. History of inadequate response to topical pharmacological treatments. Inadequate response is defined as failure to achieve stable long-term disease control after using at least one intermediate-potency TCS for at least 4 weeks or the maximum duration recommended in the product prescribing information (e.g., 14 days for super-potent TCS, whichever is shorter) within 6 months of screening. 7. Willing and able to comply with all interview and study-related procedures and questionnaires. 8. Female participants of childbearing potential should abstain from drugs or use highly effective contraceptive measures. 9. Parents or legal guardians must be able to read, understand, and give documented informed consent for the child's participation in this research.

[0099] Exclusion Criteria: Participants will be excluded from the study if they meet any of the following criteria: 1. Currently enrolled in or have participated within the past 8 weeks in a clinical study or any other type of medical research involving a research intervention that is considered scientifically or medically incompatible with this study. 2. Receiving the following treatments before the baseline visit: a. Investigational drug with a half-life of less than 8 weeks or less than 5 (whichever is longer). b. Use of Dupilumab within 8 weeks. NOTE: Enrollment of participants with prior exposure to dupilumab will be limited to <20%. c. Use of B-cell depleting biologics (including rituximab) within 6 months or until lymphocyte and CD19+ lymphocyte counts return to normal, whichever is longer. d. 5 half-lives (if known) or 16 weeks (whichever is longer) for other biological agents. 3. Has been previously randomized in any other study investigating levitra. 4. Allergy to the active substance or any excipients. 5. Use of topical study medication within 2 weeks prior to the baseline visit. 6. Significant adverse effects to TCS, such as intolerance to treatment, allergic reactions, severe skin atrophy, and systemic effects, as assessed by the investigator or treating physician will further exclude use during the study. 7. Treatment with any of the following medications within 4 weeks prior to the baseline visit, or any condition that the investigator believes may require such treatment within the first 4 weeks of study treatment: a. Immunosuppressive / immunomodulatory drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate mofetil, IFN-γ, JAK inhibitors, azathioprine, methotrexate). b. Phototherapy and photochemotherapy for AD. 8. Regular use (more than 2 visits per week) of the solarium / parlor within 4 weeks of the screening visit. 9. Use cannabis or cannabinoids to treat pruritus, pain, and AD. 10. Currently receiving cumulative doses of allergen immunotherapy (allergy shots). 11. Received BCG vaccination or treatment within 4 weeks before randomization. 12. Receipt of any live vaccine (i.e., live attenuated vaccine) within 4 weeks prior to randomization or planning to receive live vaccination during the study. 13. Within 2 weeks before screening and before the randomization visit, participants currently or recently had an acute active infection that required treatment with systemic antibiotics, antiviral drugs, antiparasitic drugs, antiprotozoal drugs, or antifungal drugs. Participants must not have symptoms or signs of confirmed or suspected infection and must have completed any appropriate anti-infection treatment. 14. Suffered from any of the following infections within 3 months before screening, or had any infection before baseline: a. Severe (requiring hospitalization, and / or treatment with intravenous or equivalent oral antibiotics); b. Opportunistic infections (as defined in Winthrop et al., Ann Rheum Dis. 2015;74(12):2107–2116). Note: Herpes zoster is considered active and will persist until all blisters have dried and crusted. c. Recurrent (including but not limited to recurrent cellulitis or chronic osteomyelitis). 15. Have HIV infection. 16. Have current or chronic infection with HBV, i.e. HBsAg positive and / or HBV DNA PCR positive. 17. Have current infection with HCV, i.e., HCV RNA positive. 18. Have known active tuberculosis infection. 19. Have a known active internal parasitic infection or are at high risk for these infections. 20. Have a history of, or have an underlying disease or surgical, physical, psychological or medical condition that, in the opinion of the investigator, would potentially affect the safety of participants in the study or interfere with the interpretation of the data. 21. Any of the following specific abnormalities on screening laboratory tests: a. AST or ALT ≥ 2x upper limit of normal (ULN) b. ALP ≥ 2×ULN (Note: If there are no other signs of liver, bone or other abnormalities, participants may be allowed to enroll, but the case must be discussed and judged to be clinically insignificant through medical monitoring before enrollment.) c. Total bilirubin ≥1.5×ULN (Note: If there is no other evidence of liver or other abnormalities, participants may be allowed to enroll, but the case must be discussed and judged to be clinically insignificant by medical monitoring before enrollment.) d. Total white blood cell count <2500 cells / μL (<2.50 x 10 3 / μL or <2.50GI / L) 22. Uncontrolled chronic illness that may require a burst of oral corticosteroids. 23. Uncontrolled asthma as defined by: a. Use of systemic steroids (oral or injectable) for asthma symptoms within the past 6 months, or b. Visited an emergency room, hospital, urgent care, or physician for uncontrolled asthma symptoms (cough, wheezing, chest tightness, wheezing) within the past 6 months, or c. Use of rescue inhaler or nebulizer more than twice a week for asthma symptoms not related to exercise in at least one month (in the past 6 months), or d. Waking up more than twice a month at night due to asthma symptoms (coughing, wheezing, breathlessness) 24. Clinically significant laboratory results outside the reference range at the Screening Visit, in the opinion of the Investigator. 25. The presence of skin comorbidities that may interfere with study assessments. 26. History of long-term alcohol abuse, intravenous drug abuse or other illegal drug abuse within 2 years before screening. 27. History of malignancy, including mycosis fungoides, within 5 years prior to the screening visit. (Exceptions: completely treated carcinoma in situ of the cervix, or completely treated and cured non-metastatic squamous or basal cell skin cancer.) 28. Pregnant or breastfeeding or planning to become pregnant or breastfeeding during the study. 29. According to the researcher’s opinion, it is not suitable for inclusion in the study. Example 2. A Phase 3, Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety of Levitra in Participants 6 Months to <18 Years with Moderate to Severe Atopic Dermatitis (KGBJ)

[0100] This open-label, Phase 3 study is designed to evaluate the long-term safety of lebrikizumab in participants aged 6 months to <18 years with moderate to severe atopic dermatitis. Participants who have completed the KGBI study (see Example 1) to Week 16 without the need for systemic rescue medication are eligible to participate in this KGBJ study.

[0101] Goals and End Points:

[0102] The following primary, secondary, and exploratory objectives and endpoints were assessed for this study. Statistical analyses were performed for the primary endpoint and key secondary endpoints. Table 5. Goals and endpoints of KGBJ

[0103] Study Design:

[0104] This is an open-label, phase 3 study designed to evaluate the long-term safety of lebrikizumab in participants aged 6 months to <18 years with moderate to severe AD.

[0105] Participants who completed the KGBI study through week 16 without requiring systemic rescue medication were eligible to participate in the KGBJ study. This study was designed to evaluate the long-term safety of lebrikizumab in moderate-to-severe atopic dermatitis.

[0106] Participants will be considered enrolled once all baseline procedures have been completed and the investigators have determined that the participant meets the inclusion and exclusion criteria. The planned treatment duration for each participant is approximately 52 weeks. All participants will enter the post-treatment follow-up period 12 weeks after the last administration of lebronizumab.

[0107] Table 6 describes the dose and frequency of levitra used in this clinical study. Table 6. Levitra doses in KGBJ

[0108] Patient population:

[0109] Approximately 250 participants will be enrolled to receive lebrinomab.

[0110] Inclusion Criteria: Participants were eligible for the study only if they met all of the following criteria: 1. Receiving treatment in the KGBI study and fully completing study treatment and the last visit in the KGBI study. 2. For female participants of childbearing potential, please use highly effective contraceptive measures that comply with local regulations. 3. Willing and able to comply with all clinic visit and study related procedures and questionnaires. 4. Provide written informed consent.

[0111] Exclusion Criteria: Participants will be excluded from the study if they meet any of the following criteria: 1. A serious adverse event (SAE) thought to be related to levitra occurs during participation in the KGBI study, and the investigator or medical monitor believes that this may indicate that continued treatment with levitra may pose an unreasonable risk to the participant*. 2. An adverse event (AE) considered to be related to levitra occurred during participation in the KGBI study and led to discontinuation of study treatment, and the investigator or medical monitor believed that this may indicate that continued treatment with levitra may pose an unreasonable risk to the participant * . 3. Meets protocol-defined criteria for permanent discontinuation of study drug in the KGBI study if deemed related to levitra or results in investigator or sponsor-initiated participant withdrawal from the study (e.g., non-compliance, inability to complete study assessments) * . * Note for Exclusion Criteria 1-3: If the KGBI study remains blinded at the time of transfer to the KGBJ study, conditions considered to be related to study treatment will be considered to be lebronizumab-related. 4. Pregnant or breastfeeding or planning to become pregnant or breastfeeding during the study.

Claims

1. A method of treating moderate to severe atopic dermatitis in a patient in need thereof, the method comprising administering levitra to the patient, wherein the patient is between 6 months and 12 years old and weighs at least 6 kilograms (kg).

2. A method for treating moderate to severe atopic dermatitis, the method comprising: Patients aged 6 months to 12 years with moderate to severe atopic dermatitis and weighing at least 6 kg were selected. Levitra is administered to the patient.

3. A method of treating moderate to severe atopic dermatitis in a patient in need thereof, the method comprising administering levitra to the patient, wherein the patient is between 12 and 18 years old and weighs less than 40 kg.

4. A method for treating moderate to severe atopic dermatitis, the method comprising: Patients aged 12 to 18 years with moderate to severe atopic dermatitis and weighing less than 40 kg were selected, and Levitra is administered to the patient.

5. The method according to any one of claims 1 to 4, wherein the patient is treated for a treatment period of 16 weeks.

6. The method according to any one of claims 1 to 5, wherein when the patient has a body weight of 6 kg to less than 15 kg, levitra is administered to the patient at 125 mg at week 0, and levitra is administered to the patient at 125 mg once every four weeks from week 2 to week 14.

7. The method according to any one of claims 1 to 5, wherein when the patient has a body weight of 15 kg to less than 40 kg, levitra is administered to the patient at 250 mg at week 0, and levitra is administered to the patient at 250 mg once every four weeks from week 2 to week 14.

8. The method according to any one of claims 1, 2 or 5, wherein when the patient has a body weight of 40 kg or more, levitra is administered to the patient at 500 mg at weeks 0 and 2, and levitra is administered to the patient at 250 mg once every two weeks from week 4 to week 14.

9. A method for treating moderate to severe atopic dermatitis, the method comprising: Patients with moderate to severe atopic dermatitis and weighing 6 kg to less than 15 kg were selected, and Patients were administered levitra at 125 mg at week 0 and every four weeks from week 2 to week 14.

10. A method for treating moderate to severe atopic dermatitis, the method comprising: Patients with moderate to severe atopic dermatitis and weighing 15 kg to less than 40 kg were selected, and Patients were administered levitra at 250 mg at week 0 and every four weeks from week 2 to week 14 at 250 mg.

11. A method for treating moderate to severe atopic dermatitis, the method comprising: Select patients with moderate to severe atopic dermatitis and weighing 40 kg or more, and Patients were administered levitra at 500 mg at weeks 0 and 2, and 250 mg every two weeks from weeks 4 to 14.

12. The method according to any one of claims 9-11, wherein the patient is between 6 months and 12 years old.

13. The method according to any one of claims 9-10, wherein the patient is between 12 and 18 years old.

14. The method according to any one of claims 1-13, wherein the patient has an Eczema Area and Severity Index (EASI) score of 16 or greater, an Investigator Global Assessment (IGA) score of 3 or greater, and more than 10% of body surface area (BSA) is affected by atopic dermatitis prior to administration of lebrikizumab.

15. The method according to any one of claims 1-14, wherein the patient has had an inadequate response to topical corticosteroids prior to administration of lebrikizumab.

16. The method according to any one of claims 1 to 15, wherein when the patient is 6 years of age or older, the patient has suffered from atopic dermatitis for at least 12 months.

17. The method according to any one of claims 1, 2, 5-12 or 14-15, wherein the patient has suffered from atopic dermatitis for at least 6 months when the patient is 6 months to less than 6 years old.

18. The method according to any one of claims 1-17, wherein kinizumab is administered to the patient subcutaneously.

19. The method according to any one of claims 1-18, further comprising determining the patient's EASI score at week 16.

20. The method according to claim 19, wherein the EASI score determined at week 16 is reduced by 75% or more compared to the EASI score determined prior to administration of lebrikizumab.

21. The method according to claim 19, wherein the EASI score determined at week 16 is reduced by 90% or more compared to the EASI score determined before administration of lebrikizumab.

22. The method according to any one of claims 1-21, further comprising determining the patient's IGA score at week 16.

23. The method according to claim 22, wherein the IGA score determined at week 16 is 0 or 1, and the IGA score determined at week 16 is reduced by 2 points or more compared to the IGA score determined before administration of lebrikizumab.

24. The method according to any one of claims 1-23, further comprising determining the patient's Numerical Rating Scale (NRS) score for Pruritus at week 16.

25. The method according to claim 24, wherein the pruritus NRS score determined at week 16 is reduced by 4 points or more compared to the pruritus NRS score determined before administration of lebrikizumab.

26. The method according to any one of claims 1-25, further comprising determining one or more of the following characteristics of the patient at week 16: i. The percentage of BSA affected by atopic dermatitis; ii. DLQI, cDLQI and / or IDLQI; ⅲ.PRISM; ⅳ.SCORAD; v. PROMIS anxiety, PROMIS depression, PROMIS sleep disorder and / or PROMIS sleep-related impairment; ⅵ.POEM; ⅶ.EQ-5D-Y and / or EQ-5D-5L; ⅷ.mSQAAQ; ⅸ.DFI; ⅹ. WPAI-AD-CG.

27. The method according to any one of claims 1-26, wherein kinizumab is administered to the patient using a subcutaneous administration device.

28. The method according to claim 27, wherein the subcutaneous administration device is selected from a prefilled syringe, a disposable pen injection device, a microneedle device, a microinfusion device, a needle-free injection device or an autoinjector device.

29. The method according to any one of claims 1-28, wherein the method further comprises administering to the patient one or more topical corticosteroids.

30. The method according to claim 29, wherein the one or more topical corticosteroids is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone.

31. The method according to claim 29 or 30, wherein one or more topical corticosteroids are administered concurrently with lebrikizumab.

32. Levitra for the treatment of moderate to severe atopic dermatitis in patients 6 months to 12 years of age weighing at least 6 kg.

33. Levitra for the treatment of moderate to severe atopic dermatitis in patients aged 12 to 18 years weighing less than 40 kg.

34. Levitra for use according to any one of claims 32 or 33, wherein the patient is treated for a treatment period of 16 weeks.

35. Levitra for use according to any one of claims 32-34, wherein when the patient has a body weight of 6 kg to less than 15 kg, the patient is administered Levitra at 125 mg at week 0, and the patient is administered Levitra at 125 mg once every four weeks from week 2 to week 14.

36. Levitra for use according to any one of claims 32-34, wherein when the patient has a body weight of 15 kg to less than 40 kg, the patient is administered Levitra at 250 mg at week 0, and the patient is administered Levitra at 250 mg once every four weeks from week 2 to week 14.

37. Levitra for use according to any one of claims 32 or 34, wherein when the patient has a body weight of 40 kg or more, the patient is administered Levitra at 500 mg in weeks 0 and 2, and is administered Levitra at 250 mg once every two weeks from week 4 to week 14.

38. Levitra for use in the treatment of moderate to severe atopic dermatitis in patients weighing 6 kg to less than 15 kg, wherein the patient will be administered levitra at 125 mg at week 0 and levitra once every four weeks from week 2 to week 14.

39. Levitra for use in the treatment of moderate to severe atopic dermatitis in patients weighing 15 kg to less than 40 kg, wherein the patient will be administered Levitra at 250 mg at week 0 and 250 mg once every four weeks from week 2 to week 14.

40. Levitra for use in the treatment of moderate to severe atopic dermatitis in patients weighing 40 kg or more, wherein the patient will be administered levitra at 500 mg in weeks 0 and 2, and levitra at 250 mg once every two weeks from weeks 4 to 14.

41. Lebrikizumab for use according to any one of claims 38-40, wherein the patient is between 6 months and 12 years old.

42. Lebrikizumab for use according to any one of claims 38-39, wherein the patient is between 12 and 18 years old.

43. Levitra for use according to any one of claims 32-42, wherein the patient has an Eczema Area and Severity Index (EASI) score of 16 or greater, an Investigator Global Assessment (IGA) score of 3 or greater, and more than 10% of body surface area (BSA) is affected by atopic dermatitis prior to administration of Levitra.

44. Levitra for use according to any one of claims 32-43, wherein the patient has had an inadequate response to topical corticosteroids prior to administration of Levitra.

45. Levitra for use according to any one of claims 32-44, wherein when the patient is 6 years of age or older, the patient has suffered from atopic dermatitis for at least 12 months.

46. ​​Levitra for use according to any one of claims 32, 34-41 or 43-44, wherein the patient has suffered from atopic dermatitis for at least 6 months when the patient is 6 months to less than 6 years old.

47. Levitra for use according to any one of claims 32-46, wherein the Levitra is administered to the patient subcutaneously.

48. Levitra for use according to any one of claims 32 to 47, wherein One or more topical corticosteroids are also administered to the patient.

49. Levitra for use according to claim 48, wherein the one or more topical corticosteroids is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone.

50. Lebrikizumab for use according to claim 48 or 49, wherein one or more topical corticosteroids are administered simultaneously with the lebrikizumab.

51. Use of levitra for the preparation of a medicament for the treatment of moderate to severe atopic dermatitis in patients aged 6 months to 12 years and weighing at least 6 kg.

52. Use of levitra for the preparation of a medicament for the treatment of moderate to severe atopic dermatitis in patients aged 12 to 18 years and weighing less than 40 kg.

53. Use of levitra in the preparation of a medicament for treating moderate to severe atopic dermatitis in patients weighing 6 kg to less than 15 kg, wherein levitra is administered to the patient at 125 mg in week 0 and 125 mg once every four weeks from week 2 to week 14.

54. Use of levitra in the preparation of a medicament for treating moderate to severe atopic dermatitis in patients weighing 15 kg to less than 40 kg, wherein levitra is administered to the patient at 250 mg in week 0 and 250 mg once every four weeks from week 2 to week 14.

55. Use of levitra in the preparation of a medicament for treating moderate to severe atopic dermatitis in a patient weighing 40 kg or more, wherein levitra is administered to the patient at 500 mg in weeks 0 and 2, and 250 mg once every two weeks from week 4 to week 14.

56. A pharmaceutical composition comprising lebrikizumab for use in the treatment of moderate to severe atopic dermatitis in patients aged 6 months to 12 years and weighing at least 6 kg.

57. A pharmaceutical composition comprising lebrikizumab for use in the treatment of moderate to severe atopic dermatitis in patients aged 12 to 18 years and weighing less than 40 kg.

58. A pharmaceutical composition comprising levitra for the treatment of moderate to severe atopic dermatitis in patients weighing 6 kg to less than 15 kg, wherein levitra is administered to the patient at 125 mg at week 0 and 125 mg once every four weeks from week 2 to week 14.

59. A pharmaceutical composition comprising levitra for the treatment of moderate to severe atopic dermatitis in patients weighing 15 kg to less than 40 kg, wherein levitra is administered to the patient at 250 mg at week 0 and 250 mg once every four weeks from week 2 to week 14.

60. A pharmaceutical composition comprising levitra for the treatment of moderate to severe atopic dermatitis in patients weighing 40 kg or more, wherein levitra is administered to the patient at 500 mg in weeks 0 and 2, and 250 mg once every two weeks from weeks 4 to 14.

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