IL-13 antibody for the treatment of atopic dermatitis

Abstract

The present invention provides a method for treating atopic dermatitis or reducing itching associated with atopic dermatitis. [Solution] A method for treating atopic dermatitis or reducing itching associated with atopic dermatitis comprises administering to the patient a pharmaceutical composition containing an antibody that binds to human IL-13 ("anti-IL-13 antibody"). Dosages and administration regimens for the use of the anti-IL-13 antibody are also provided.

Description

Technical Field

[0001] The present invention relates to methods, the use of antibodies that bind to human IL-13 ("anti-IL-13 antibodies"), and pharmaceutical compositions for treating atopic dermatitis or reducing pruritus associated with atopic dermatitis. The present invention also relates to methods for treating atopic dermatitis or reducing pruritus associated with atopic dermatitis, and dosages and administration regimens for the use of anti-IL-13 antibodies.

Background Art

[0002] Atopic dermatitis (AD) is a chronic relapsing and remitting inflammatory skin disorder that affects all age groups. Clinically, AD is characterized by dryness, erythematous crusted rash, lichenification, skin barrier impairment, and intense pruritus (Bieber T., N Engl J Med 2008;358:1483-94). The disease burden of patients with AD is high, and their quality of life is significantly affected. In one study, AD was shown to have a greater negative effect on the mental health of patients than diabetes and hypertension (Zuberbier T, et al., J Allergy Clin Immunol 2006;118:226-32). Patients with moderate to severe AD have a higher prevalence of social dysfunction and sleep disturbances, which is directly related to the severity of the disease (Williams H, et al., J Allergy Clin Immunol 2008;121:947-54.e15). Depression, anxiety, and social dysfunction affect not only AD patients but also their caregivers (Zuberbier T, et al., J Allergy Clin Immunol 2006;118:226-32).

[0003] Interleukin (IL)-13 is a key mediator of T-helper type 2 (Th2) inflammation and signals via the heterodimeric receptor IL-4Rα / IL-13Rα1. Several pieces of evidence suggest that IL-13 is a crucial pathogenic component in Alzheimer's disease (AD). Increased IL-13 expression has been consistently reported in AD skin (Hamid Q, et al., J Allergy Clin Immunol 98:225-31

[1996] , Jeong CW, et al., Clin Exp Allergy 33:1717-24

[2003] , Tazawa T, et al., Arch Dermatol Res 295:459-64

[2004] , Neis MM, et al., J Allergy Clin Immunol 118:930-7

[2006] , Suarez-Farinas M, et al., J Allergy Clin Immunol 132:361-70

[2013] , Choy DF, et al., J Allergy Clin Several reports suggest a relationship between IL-13 expression and disease severity (Immunol. 130:1335-43

[2012] , La Grutta S, et al., Allergy 60:391-5

[2005] ). Increased levels of IL-13 have also been reported in the serum of AD patients (Novak N, et al., J Invest Dermatol 2002;119:870-5, International Publication No. 2016149276), and several studies have reported increased levels of IL-13-expressing T cells in the blood of AD patients (Akdis M, et al., J Immunol 1997;159:4611-9, Aleksza M, et al., Br J Dermatol 2002;147:1135-41, La Grutta S, et al., Allergy 2005;60:391-5).

[0004] Treatment approaches for Alzheimer's disease (AD) primarily include trigger avoidance, skin hydration through bathing, and the use of anti-inflammatory therapies such as emollients and topical corticosteroids (TCS). In many patients, treatment with TCS provides some symptom relief but does not adequately control the patient's disease. In addition, the use of TCS is associated with many comorbidities and limitations, including a high patient burden. Long-term use of TCS is not recommended due to the risk of cutaneous atrophy, hyperpigmentation abnormalities, acneiform rash, and systemic absorption (e.g., hypothalamic-pituitary axial effect, Cushing's disease).

[0005] For patients with persistent moderate to severe Alzheimer's disease (AD) who do not respond well to TCS, several step-up treatment options are available (Ring J, et al., J Eur Acad Dermatol Venereol 2012;26:1176-93, Schneider L, et al., J Allergy Clin Immunol 2013;131:295-9.e1-27). These step-up options include topical calcineurin inhibitors, phototherapy, and immunosuppressants such as oral corticosteroids, cyclosporine, azathioprine, methotrexate, and mycophenolate. Of these, cyclosporine is approved for the treatment of moderate to severe AD in many European countries, but is not approved in the United States, where its use is limited to patients 16 years of age or older (up to 8 weeks of [NEORAL®]). Even when cyclosporine shows substantial efficacy, approximately 50% of patients relapse within two weeks and 80% within six weeks after discontinuation of therapy (Amor KT, et al., J Am Acad Dermatol 2010;63:925-46). Cyclosporine A (CsA) is a potent immunosuppressant that affects both humoral and cellular immune responses, potentially leading to increased susceptibility to infection and decreased cancer immune surveillance. Other commonly recognized toxicities of CsA include hypertension and renal and hepatic impairment. In addition, CsA may interact with other commonly used medications, potentially affecting their metabolism and effects.

[0006] There remains an unmet medical need for safer and more effective therapies and treatment regimens for patients with moderate to severe Alzheimer's disease (AD), particularly those whose AD is not adequately controlled with cyclosporine or for whom cyclosporine is not medically recommended. There is also a need for therapeutic interventions and regimens that offer an improved safety profile with limited toxicity compared to existing treatments, or that provide greater tolerability or convenience to patients, thereby improving patient compliance. [Overview of the project]

[0007] Methods, the use of anti-IL-13 antibodies such as lebrikizumab, and pharmaceutical compositions for treating atopic dermatitis or reducing pruritus associated with atopic dermatitis are provided herein. Doses and administration regimens for methods and the use of anti-IL-13 antibodies such as lebrikizumab for treating atopic dermatitis or reducing pruritus associated with atopic dermatitis are also provided herein. In some embodiments, methods and the use of anti-IL-13 antibodies for treating atopic dermatitis or reducing pruritus associated with atopic dermatitis are provided herein in patients with moderate to severe atopic dermatitis that is not adequately controlled with cyclosporine (e.g., insufficient response to or intolerance to cyclosporine) or for which cyclosporine is not medically recommended.

[0008] In one embodiment, a method is provided herein for treating moderate to severe atopic dermatitis or reducing pruritus associated with atopic dermatitis in a patient who has shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended, and this method includes administering to the patient a pharmaceutical composition comprising an anti-IL-13 antibody. In some embodiments, a method is provided herein for treating moderate to severe atopic dermatitis or reducing pruritus, which includes selecting a patient who has moderate to severe atopic dermatitis and has shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended, and administering to the patient a pharmaceutical composition comprising an antibody that binds to human IL-13. In some embodiments, the patient is 12 years of age or older. In some embodiments, the patient has had moderate to severe atopic dermatitis for at least one year. In some embodiments, the patient has an Eczema Area and Severity Index (EASI) score of 16 or higher, an Investigator Global Assessment (IGA) score of 3 or higher, and a body surface area (BSA) affected by more than 10% atopic dermatitis prior to administration of the pharmaceutical composition.

[0009] Furthermore, methods for treating moderate to severe atopic dermatitis or reducing pruritus associated with atopic dermatitis are provided herein, which include selecting patients who (i) are 12 years of age or older, (ii) have had chronic atopic dermatitis for more than one year according to the Hanifin and Rajka criteria, (iii) have an EASI score of 16 or higher, (iv) have an IGA score of 3 or higher, (v) more than 10% of BSA are affected by atopic dermatitis, (vi) have shown an inadequate response to topical corticosteroids, and (vii) have shown an inadequate response to or intolerance to cyclosporine, or for which cyclosporine is not medically recommended for the patient, and administering to the patient a pharmaceutical composition containing an antibody that binds to human IL-13.

[0010] In some embodiments, cyclosporine is cyclosporine A (CsA). In some embodiments, the patient showed an inadequate response to cyclosporine (e.g., CsA) at least four weeks prior to administration of the pharmaceutical composition. In some embodiments, the patient showed intolerance to cyclosporine (e.g., CsA). In some embodiments, cyclosporine is not medically recommended for the patient for any of the following reasons: (i) medical contraindications, (ii) use of prohibited concomitant medications, (iii) increased susceptibility to cyclosporine-induced renal impairment and / or hepatic injury, (iv) increased risk of serious infection, or (v) hypersensitivity to the cyclosporine active substance or excipients. In some embodiments, the patient showed an inadequate response to topical corticosteroids.

[0011] In some embodiments, the anti-IL-13 antibody binds to IL-13 with high affinity and blocks signaling via the active IL-4R alpha / IL-13R alpha 1 heterodimer. In some embodiments, the anti-IL-13 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the VH comprises HCDR1 containing SEQ ID NO: 1, HCDR2 containing SEQ ID NO: 2, and HCDR3 containing SEQ ID NO: 3, and the VL comprises LCDR1 containing SEQ ID NO: 4, LCDR2 containing SEQ ID NO: 5, and LCDR3 containing SEQ ID NO: 6. In some embodiments, the anti-IL-13 antibody comprises a VH containing SEQ ID NO: 7 and a VL containing SEQ ID NO: 8. In some embodiments, the anti-IL-13 antibody comprises a heavy chain containing SEQ ID NO: 9 and a light chain containing SEQ ID NO: 10. In some embodiments, the anti-IL-13 antibody is lebrikizumab.

[0012] In some embodiments, the pharmaceutical composition contains 250 mg or 500 mg of anti-IL-13 antibody. In some embodiments, the pharmaceutical composition is administered subcutaneously to the patient.

[0013] In some embodiments, the patient is treated with the pharmaceutical composition over a period of approximately 16 to 52 weeks. In some embodiments, the patient is treated with the pharmaceutical composition for a treatment period (or induction period), for example, approximately 16 weeks. During this 16-week treatment period, the patient is treated with a loading dose pharmaceutical composition containing 500 mg of antibody in two doses, once every two weeks, and a subsequent dose pharmaceutical composition containing 250 mg of antibody in seven doses, once every two weeks.

[0014] After the completion of the treatment or induction period, the patient enters a maintenance period, for example, up to 36 weeks. In some embodiments, the patient is treated during the maintenance period with a maintenance dose pharmaceutical composition containing 250 mg of antibody once every two weeks.

[0015] In another embodiment, pharmaceutical compositions comprising an anti-IL-13 antibody are provided herein for use in the treatment of moderate to severe atopic dermatitis or reduction of pruritus in patients who have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended. Also provided herein are pharmaceutical compositions comprising an anti-IL-13 antibody for use in the treatment of moderate to severe atopic dermatitis or reduction of pruritus in patients who (i) are 12 years of age or older, (ii) have had chronic atopic dermatitis for more than one year according to the Hanifin and Rajka criteria, (iii) have an EASI score of 16 or higher, (iv) have an IGA score of 3 or higher, (v) more than 10% of BSA are affected by atopic dermatitis, (vi) have shown an inadequate response to topical corticosteroids, and (vii) have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended. In some embodiments, the pharmaceutical compositions are intended for subcutaneous administration to the patient.

[0016] In another embodiment, the use of a pharmaceutical composition containing an anti-IL-13 antibody in the manufacture of a drug for the treatment of moderate to severe atopic dermatitis or for the reduction of pruritus in patients who have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended. Also provided herein is the use of a pharmaceutical composition containing an anti-IL-13 antibody in the manufacture of a drug for the treatment of moderate to severe atopic dermatitis or for the reduction of pruritus in patients who (i) are 12 years of age or older, (ii) have had chronic atopic dermatitis for more than one year according to the Hanifin and Rajka criteria, (iii) have an EASI score of 16 or higher, (iv) have an IGA score of 3 or higher, (v) more than 10% of BSA are affected by atopic dermatitis, (vi) have shown an inadequate response to topical corticosteroids, and (vii) have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended. In some embodiments, the pharmaceutical composition is for subcutaneous administration to the patient.

[0017] In some embodiments, the methods, uses, and pharmaceutical compositions described herein further include administering one or more topical corticosteroids to a patient. In some embodiments, the topical corticosteroid is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone. In some embodiments, the topical corticosteroid is administered concurrently with an anti-IL-13 antibody. [Brief explanation of the drawing]

[0018] [Figure 1] This is a schematic diagram of the Phase 3 study design described in Example 1. [Modes for carrying out the invention]

[0019] Methods, uses of anti-IL-13 antibodies, and pharmaceutical compositions for treating atopic dermatitis or reducing pruritus associated with atopic dermatitis are provided herein. Doses and administration regimens for methods and uses of anti-IL-13 antibodies for treating atopic dermatitis or reducing pruritus associated with atopic dermatitis are also provided herein. In some embodiments, methods and uses of anti-IL-13 antibodies for treating atopic dermatitis or reducing pruritus associated with atopic dermatitis are provided herein in patients with moderate to severe atopic dermatitis that is not adequately controlled with cyclosporine (e.g., insufficient response to or intolerance to cyclosporine) or for which cyclosporine is not medically recommended.

[0020] In one embodiment, a method is provided herein for treating moderate to severe atopic dermatitis or reducing pruritus associated with atopic dermatitis in patients who have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended, which includes administering to the patient a pharmaceutical composition comprising an anti-IL-13 antibody. In some embodiments, a method is provided herein for treating moderate to severe atopic dermatitis or reducing pruritus, which includes selecting a patient who has moderate to severe atopic dermatitis and has shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended, and administering to the patient a pharmaceutical composition comprising an antibody that binds to human IL-13. In some embodiments, the patient is 12 years of age or older. In some embodiments, the patient has had moderate to severe atopic dermatitis for at least one year. In some embodiments, the patient has a BSA with an EASI score of 16 or higher, an IGA score of 3 or higher, and more than 10% atopic dermatitis prior to administration of the pharmaceutical composition.

[0021] Furthermore, methods for treating moderate to severe atopic dermatitis or reducing pruritus associated with atopic dermatitis are provided herein, which include selecting patients who (i) are 12 years of age or older, (ii) have had chronic atopic dermatitis for more than one year according to the Hanifin and Rajka criteria, (iii) have an EASI score of 16 or higher, (iv) have an IGA score of 3 or higher, (v) more than 10% of BSA are affected by atopic dermatitis, (vi) have shown an inadequate response to topical corticosteroids, and (vii) have shown an inadequate response to or intolerance to cyclosporine, or for which cyclosporine is not medically recommended for the patient, and administering to the patient a pharmaceutical composition containing an antibody that binds to human IL-13.

[0022] In some embodiments, cyclosporine is cyclosporine A (CsA). In some embodiments, the patient showed an inadequate response to cyclosporine (e.g., CsA) at least four weeks prior to administration of the pharmaceutical composition. In some embodiments, the patient showed intolerance to cyclosporine (e.g., CsA). In some embodiments, cyclosporine is not medically recommended for the patient for any of the following reasons: (i) medical contraindications, (ii) use of prohibited concomitant medications, (iii) increased susceptibility to cyclosporine-induced renal impairment and / or hepatic injury, (iv) increased risk of serious infection, or (v) hypersensitivity to the cyclosporine active substance or excipients. In some embodiments, the patient showed an inadequate response to topical corticosteroids.

[0023] In some embodiments, the patient has been previously exposed to dupilumab, an anti-IL-4Rα monoclonal antibody used to treat moderate to severe atopic dermatitis. In some embodiments, the patient has not been previously exposed to dupilumab.

[0024] In some embodiments, moderate to severe atopic dermatitis can be determined by the Hanifin and Rajka criteria. The Hanifin and Rajka diagnostic criteria are described in Acta Derm Venereol (Stockh) 1980; Suppl 92: 44-7. To establish a diagnosis of atopic dermatitis, a patient requires the presence of at least three of the following "essential features" and three or more secondary features. Essential features include intense pruritus, typical morphology and distribution such as flexural lichenification or linearity, chronic or chronic-recurrent dermatitis, and a personal or family history of atopy, such as asthma, allergic rhinitis, atopic dermatitis. Secondary features include xerosis, ichthyosis, palmoplantar hyperlinearity, or keratosis pilaris, immediate-type (type I) skin test reactivity, elevated serum IgE, onset at a young age, tendency to skin infections (especially S. aureus and herpes simplex), cellular immunodeficiency, tendency to non-specific hand or foot dermatitis, nipple eczema, cheilitis, recurrent conjunctivitis, Dennie-Morgan infraorbital fold, keratoconus, anterior subcapsular cataract, infraorbital darkening, facial pallor / facial erythema, pityriasis alba, anterior cervical fold, and pruritus during sweating. Further secondary criteria include intolerance to wool and fat solvents, perifollicular accentuation, food intolerance, course influenced by environmental or emotional factors, and white dermographism / delayed blanching.

[0025] The severity of atopic dermatitis can also be determined by the "Rajka and Langeland diagnostic criteria," as described in Rajka G and Langeland T, Acta Derm Venereol (Stockh) 1989;144(Suppl):13-4. The three disease severity assessment categories are scored from 1 to 3: i) the extent of the affected body area, ii) the course (e.g., more or less than 3 months in a year, or continuous course), and iii) the intensity of itching, ranging from mild to severe (usually disrupting nighttime sleep). A score of 1.5 or 2.5 is acceptable. The overall disease severity is determined by the sum of the individual scores from the three disease assessment categories, with mild being defined as a sum of 3-4, moderate as a score of 4.5-7.5, and severe as a sum of 8-9.

[0026] The anti-IL-13 antibodies suitable for use in the methods and uses provided herein have been previously described, for example, in WO 2005 / 062967. In some embodiments, the anti-IL-13 antibody binds to IL-13 with high affinity and blocks signaling through the active IL-4R alpha / IL-13R alpha1 heterodimer. In some embodiments, the anti-IL-13 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein VH comprises HCDR1 comprising SEQ ID NO: 1, HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3, and VL comprises LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO: 5, and LCDR3 comprising SEQ ID NO: 6. In some embodiments, the anti-IL-13 antibody comprises a VH comprising SEQ ID NO: 7 and a VL comprising SEQ ID NO: 8. In some embodiments, the anti-IL-13 antibody comprises a heavy chain comprising SEQ ID NO: 9 and a light chain comprising SEQ ID NO: 10. In some embodiments, the anti-IL-13 antibody is lebrikizumab. The amino acid sequence of lebrikizumab is provided in Table 1. Truncation of the C-terminus of an IgG antibody can occur when one or two C-terminal amino acids are removed from the heavy chain of the IgG antibody. For example, if a C-terminal lysine (K) is present, it can be truncated or removed from the heavy chain. The penultimate glycine can likewise be truncated or removed from the heavy chain. Modification of the N-terminal amino acid of IgG can also occur. For example, the N-terminal glutamine (Q) or glutamic acid (E) can cyclize spontaneously to pyroglutamic acid (pE). SEQ ID NO: 9 reflects these potential modifications of the lebrikizumab heavy chain.

[0027] Table 1. Lebrikizumab Sequence

Table 1

[0028] Anti-IL-13 antibodies, such as lebrikizumab, can be formulated with appropriate carriers or excipients into pharmaceutical compositions suitable for administration to patients. For example, anti-IL-13 antibodies, such as lebrikizumab, can be formulated in pharmaceutical compositions such as those described in International Publication No. 2013 / 066866. The pharmaceutical composition may contain 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, or 500 mg of anti-IL-13 antibody. In some embodiments, the pharmaceutical composition contains 250 mg or 500 mg of anti-IL-13 antibody. In some embodiments, the concentration of anti-IL-13 antibody in the pharmaceutical composition is 100 mg / mL to 150 mg / mL, for example, 125 mg / mL. The pharmaceutical composition may also contain 5 mM to 40 mM histidine acetate buffer, pH 5.4 to 6.0. In some embodiments, the pharmaceutical composition further comprises a polyol (e.g., sugar) having a concentration of 100 mM to 200 mM, and / or a surfactant (e.g., polysorbate 20) having a concentration of 0.01% to 0.1%. In one embodiment, the pharmaceutical composition comprises 125 mg / mL of anti-IL-13 antibody (e.g., levukizumab), 20 mM histidine acetate buffer, pH 5.7, 175 mM sucrose, and 0.03% polysorbate 20.

[0029] In some embodiments, the pharmaceutical composition is administered subcutaneously to the patient. The pharmaceutical composition can be administered to the patient at a frequency of once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, or once every 8 weeks. In some embodiments, the pharmaceutical composition is administered to the patient once every 2 weeks or once every 4 weeks. In some embodiments, the pharmaceutical composition containing 250 mg or 500 mg of anti-IL-13 antibody is administered subcutaneously to the patient once every 2 weeks or once every 4 weeks.

[0030] In some embodiments, the pharmaceutical composition is administered to the patient using a subcutaneous administration device. The subcutaneous administration device may be selected from pre-filled syringes, disposable pen-type injection devices, microneedle devices, microinfuser devices, needleless injection devices, or autoinjector devices. Various subcutaneous administration devices, including autoinjector devices, are known and commercially available in the art. Examples of devices include, but are not limited to, pre-filled syringes (e.g., BD HYPAK SCF®, READYFILL®, and STERIFILL SCF® from Becton Dickinson, CLEARSHOT® copolymer-filled syringes from Baxter, and Daikyo Seiko CRYSTAL ZENITH® pre-filled syringes available from West Pharmaceutical Services), disposable pen-type injection devices such as BD Pen from Becton Dickinson, ultra-sharp and microneedle devices (e.g., INJECT-EASE® and micro-infuser devices from Becton Dickinson, and H-PATCH® available from Valeritas), and needleless injection devices (e.g., BIOJECTOR® and IJECT® available from Bioject, and SOF-SERTER® and patch devices available from Medtronic). In some embodiments, the subcutaneous administration device is an automated infusion device described in International Publication No. 2008 / 112472, International Publication No. 2011 / 109205, International Publication No. 2014 / 062488, and / or International Publication No. 2016 / 089864.

[0031] In some embodiments, patients are treated with the pharmaceutical composition over a period of approximately 16 to 52 weeks, for example, 16, 20, 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0032] In some embodiments, the patient is treated with the pharmaceutical composition over a treatment period (or induction period) of approximately 16 weeks. During the 16-week treatment period, the patient is treated with a loading dose containing 500 mg of antibody in two doses every two weeks (e.g., baseline (week 0) and week 2), and a subsequent dose containing 250 mg of antibody in seven doses every two weeks (e.g., weeks 4, 6, 8, 10, 12, 14, and 16).

[0033] During and after treatment, patients may be evaluated for one or more characteristics of the Atopic Dermatitis Disease Severity Measures (ADDSM) that determine certain signs, symptoms, features, or parameters associated with atopic dermatitis that can be assessed quantitatively or qualitatively. Examples of ADDSM include the Eczema Area and Severity Index (EASI), Investigator's General Assessment (IGA), Body Surface Area (BSA), Severity Scoring of Atopic Dermatitis (SCORAD), Numerical Rating Scale (NRS), Sleep Deprivation Scale, Skin Pain NRS score, Patient-Oriented Eczema Measure (POEM) total score, Dermatology Life Quality Index (DLQI) score, Children's Dermatology Life Quality Index (CDLQI), DLQI-Relevant (DLQI-R) score, World Health Organization-5 Well-Being Index (WHO-5) score, Recap (RECAP) score for atopic eczema, and Treatment Satisfaction Questionnaire (9 items). Examples include, but are not limited to, the Satisfaction Questionnaire for Medication-9 items (TSQM-9) score.

[0034] ADDSM can be measured at baseline (before administration of the pharmaceutical composition) and at one or more time points after administration of the pharmaceutical composition. For example, ADDSM may be measured at the end of weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16 or later after the initial treatment with the pharmaceutical composition. 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 establish whether there has been an improvement (e.g., reduction) in ADDSM.

[0035] The Eczema Area and Severity Index (EASI) is a valid scale used in clinical settings to assess the severity and extent of Alzheimer's disease (AD) (Hanifin et al., Exp Dermatol. 2001;10:11-18). The EASI is a composite index with a score ranging from 0 to 72, where higher values ​​indicate more severe and / or widespread disease. The severity of erythema, induration / papulogenesis, abrasions, and lichenification can be assessed by a clinician or other healthcare professional on a scale of 0 (none) to 3 (severe) for each of the four body regions: head and neck, torso, upper extremities, and lower extremities, with half-points being acceptable. In addition, the degree of AD's involvement in each of the four body regions can be assessed as a percentage of the body surface area of ​​the head, torso, upper extremities, and lower extremities, and can be converted to a score of 0 to 6. A total score (0 to 72) is assigned based on the sum of the total scores for each of the four body regions.

[0036] The Investigator's Global Assessment (IGA) is a globally used assessment scale for evaluating the severity of a patient's Alzheimer's disease (AD) (Simpson E, et al. J Am Acad Dermatol. 2020;83(3):839-846). It is based on a 5-point scale ranging from 0 (none) to 4 (severe), and the score is selected using a descriptive word that best describes the overall appearance of the lesion at a given time (see Table 2).

[0037] Table 2. Overall evaluation by the principal investigator. [Table 2]

[0038] Body surface area (BSA) assessment estimates the degree of disease or skin involvement in Alzheimer's disease (AD) and is expressed as a percentage of total surface area. BSA is determined by a clinician or other healthcare professional using the patient's palm, with the rule being approximately 1% BSA.

[0039] The "Scoral Scoring Assessment Method for Atopic Dermatitis," or "SCORAD," is an effective clinical tool for assessing the degree and severity of AD, developed by the European Task Force on Atopic Dermatitis (Consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23-31). The assessment has three components: (i) the degree of AD is assessed as a percentage of each defined body area and reported as the sum of all areas with scores ranging from 0 to 100; (ii) the severity part of SCORAD consists of six items: redness, swelling, exudation / crusting, abrasions, skin thickening / lichenification, and dryness. Each item is graded as follows: none (0), mild (1), moderate (2), or severe (3) (maximum total of 18 points); (iii) Subjective assessments of itching and insomnia are recorded for each symptom using a visual analogue scale (VAS), where 0 is no itching (or insomnia) and 10 is the worst itching (or insomnia) imaginable (maximum possible score is 20). The formula for the SCORAD index is A / 5 + 7B / 2 + C, where A is defined as the range (0-100), B as the intensity (0-18), and C as the subjective symptom (0-20). The maximum score for the SCORAD index is 103.

[0040] The Numerical Rating Scale for Pruritus (NRS) is an 11-point scale used by patients (with the assistance of a parent / caregiver, if appropriate) to assess the severity of the worst itching over the past 24 hours, where 0 indicates "no itching" and 10 indicates "worst imaginable itching" (Phan NQ, et al. Acta Derm Venereol 2012;92:502-507). Assessments are recorded by patients using an electronic diary daily until week 16, and weekly thereafter. The baseline pruritus NRS is determined based on the mean of the daily pruritus NRS scores over the 7 days immediately preceding baseline. This calculation requires scores for at least 4 of those 7 days immediately preceding baseline.

[0041] The Skin Pain NRS is an 11-point scale completed by the patient (with the assistance of a parent / caregiver, if appropriate) to assess the worst skin pain (e.g., discomfort or burning pain) over the past 24 hours, where 0 indicates "no pain" and 10 indicates "worst imaginable pain" (Newton L, et al. J Patient Rep Outcomes. 2019 Jul 16;3:42). Assessments are recorded by the patient daily using an electronic diary until week 16, and weekly thereafter. The baseline Skin Pain NRS is determined based on the mean of the daily Skin Pain NRS scores over the 7 days immediately preceding baseline. This calculation requires scores for at least 4 of those 7 days immediately preceding baseline.

[0042] The sleep deprivation scale assesses a patient's sleep using a 5-point Likert scale (with scores ranging from 0 [none], 1 [slight], 2 [moderate], 3 [quite] to 4 [unable to sleep at all]) for sleep disturbance. It is assessed by the patient using patient-reported outcome (PRO) measures, such as an eDiary.

[0043] The Patient Oriented Eczema Measure (POEM) is a seven-item valid questionnaire completed by the patient (with the assistance of a parent / caregiver, if appropriate, to assess disease symptoms) (Centre of Evidence Based Dermatology. POEM - Patient Oriented Eczema Measure. https: / / www.nottingham.ac.uk / research / groups / cebd / resources / poem.aspx). Patients are asked to answer questions about dry skin, itching, peeling, cracking, sleep deprivation, bleeding, and exudation. All responses have equal weight, and the possible total score is 0-28 (responses are scored as follows: no day = 0, 1-2 days = 1, 3-4 days = 2, 5-6 days = 3, daily = 4). A higher score indicates a poorer quality of life. POEM responses are tracked weekly using an electronic diary.

[0044] The Dermatological Quality of Life Index (DLQI) is a 10-item valid questionnaire, completed by the patient or caregiver, used to assess the impact of skin disease on a patient's quality of life (Finlay, AY and Khan, GK 1994. Clinical and Experimental Dermatology 1993 Sep 23;19:210-216). The 10 questions cover the following topics over the past week: symptoms, distress, shopping and home care, clothing, social and leisure, sports, work or study, close relationships, sexual activity, and treatment. Each question is scored from 0 to 3 ("never," "a little," "a lot," and "very often"), resulting in a total score ranging from 0 to 30. A higher score indicates a poorer quality of life.

[0045] For adolescents under 16 years of age, the Childhood Dermatological Questionnaire (CDLQI) is used, which is based on a different set of 10 questions than the DLQI (Lewis-Jones MS, Finlay AY. British Journal of Dermatology, 1995;132:942-949).

[0046] DLQI-R is a recently developed assessment method that adjusts the total score of the DLQI questionnaire for the number of non-relevant responses (NRRs) reported by patients (Rencz F, et al. Br J Dermatol. 2020;182(5):1167-1175).

[0047] The World Health Organization-5 Wellbeing Index (WHO-5) assessment is a self-report scale of current mental well-being that covers five positively expressed items related to positive mood (energetic, relaxed), vitality (active, refreshed, restful and awake), and general interests (interested in things) (Topp CW, et al. Psychoother Psychosom. 2015;84(3):167-176.). Each item is rated on a 6-point Likert scale ranging from 0 (no time) to 5 (all time). Raw scores are converted to a score from 0 to 100, with lower scores indicating poorer well-being.

[0048] Recap (RECAP) for atopic eczema is a seven-item patient-reported assessment tool used to capture eczema control over the previous week (Howells, L., et al. British Journal of Dermatology 2019;183:524-536). Each item is scored on a 5-point Likert scale ranging from 0 (very good) to 4 (very bad). A higher score indicates a poorer experience with eczema control.

[0049] The Therapeutic Satisfaction Questionnaire-9 (TSQM-9) is a nine-item scale that assesses the most common aspects patients use to evaluate their medications (i.e., overall satisfaction, effectiveness, and convenience) (Bharmal M, et al. Health Qual Life Outcomes. 2009;7:36). Each scale is scored on a scale of 0 to 100, with higher scores indicating greater satisfaction.

[0050] In some embodiments, the patient's EASI score is determined after the treatment period, for example, at week 16. In some embodiments, the patient's EASI score determined after the treatment period is reduced by 50% or more compared to the EASI score determined before administration of the first loading dose of the antibody, which means the patient has achieved "EASI 50". In some embodiments, the patient's EASI score determined after the treatment period is reduced by 75% or more compared to the EASI score determined before administration of the first loading dose of the antibody, which means the patient has achieved "EASI 75". In some embodiments, the patient's EASI score determined after the treatment period is reduced by 90% or more compared to the EASI score determined before administration of the first loading dose of the antibody, which means the patient has achieved "EASI 90".

[0051] In some embodiments, the patient's IGA score is determined after the treatment period. In some embodiments, the patient's IGA score determined after the treatment period is 0 or 1, and the IGA score determined after the treatment period is reduced by 2 points or more compared to the IGA score determined before administration of the first loading dose of the antibody.

[0052] In some embodiments, the patient's pruritus NRS score is determined after the treatment period. In some embodiments, the patient's pruritus NRS score determined after the treatment period is reduced by 4 points or more compared to the pruritus NRS score determined before administration of the first loading dose of the antibody.

[0053] After the completion of the treatment or induction period, the patient enters a maintenance period. The maintenance period can be up to 36 weeks (e.g., approximately 4, 8, 12, 16, 20, 24, 28, 32, or 36 weeks). In some embodiments, the patient is treated with a maintenance dose pharmaceutical composition containing 250 mg of antibody every two weeks during the maintenance period.

[0054] During and after the maintenance period, patients are assessed for one or more features of the ADDSM, such as EASI, IGA, BSA, SCORAD, pruritus NRS, sleep deprivation scale, skin pain NRS score, POEM total score, DLQI score, CDLQI, DLQI-R score, WHO-5 score, RECAP score, and TSQM-9 score. The ADDSM may be measured at the start of the maintenance period and at one or more points during the maintenance period. For example, ADDSM may be measured at the end of week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 of the maintenance period. The difference between the ADDSM value at a specific point in time during the maintenance period and the ADDSM value at the start of the maintenance period is used to determine whether there has been an improvement (e.g., reduction) in ADDSM.

[0055] In some embodiments, the patient's EASI score is determined during or after the maintenance period. In some embodiments, the patient achieved EASI50, EASI75, or EASI90 during or after the maintenance period compared to the EASI score determined after the treatment period. In some embodiments, the patient's IGA score is determined during or after the maintenance period. In some embodiments, the patient's IGA score determined during or after the maintenance period is 0 or 1, and the IGA score determined during or after the maintenance period is reduced by 2 points or more compared to the IGA score determined after the treatment period. In some embodiments, the patient's pruritus NRS score is determined during or after the maintenance period. In some embodiments, the patient's pruritus NRS score determined during or after the maintenance period is reduced by 4 points or more compared to the pruritus NRS score determined after the treatment period.

[0056] In another embodiment, a pharmaceutical composition comprising an anti-IL-13 antibody is provided herein for use in the treatment of moderate to severe atopic dermatitis or reduction of pruritus in patients who have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended. Also provided herein is the use of a pharmaceutical composition comprising an anti-IL-13 antibody for use in the treatment of moderate to severe atopic dermatitis or reduction of pruritus in patients who (i) are 12 years of age or older, (ii) have had chronic atopic dermatitis for more than one year according to the Hanifin and Rajka criteria, (iii) have an EASI score of 16 or higher, (iv) have an IGA score of 3 or higher, (v) more than 10% of BSA is affected by atopic dermatitis, (vi) have shown an inadequate response to topical corticosteroids, and (vii) have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended. In some embodiments, the pharmaceutical composition is for subcutaneous administration to the patient.

[0057] In another embodiment, the use of a pharmaceutical composition containing an anti-IL-13 antibody in the manufacture of a drug for the treatment of moderate to severe atopic dermatitis or for the reduction of pruritus in patients who have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended. Also provided herein is the use of a pharmaceutical composition containing an anti-IL-13 antibody in the manufacture of a drug for the treatment of moderate to severe atopic dermatitis or for the reduction of pruritus in patients who (i) are 12 years of age or older, (ii) have had chronic atopic dermatitis for more than one year according to the Hanifin and Rajka criteria, (iii) have an EASI score of 16 or higher, (iv) have an IGA score of 3 or higher, (v) more than 10% of BSA are affected by atopic dermatitis, (vi) have shown an inadequate response to topical corticosteroids, and (vii) have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended. In some embodiments, the pharmaceutical composition is for subcutaneous administration to the patient.

[0058] In some embodiments, the methods and uses described herein further include administering one or more topical corticosteroids to a patient. Examples of topical corticosteroids include, but are not limited to, triamcinolone acetonide, hydrocortisone, and combinations of triamcinolone acetonide and hydrocortisone. Triamcinolone acetonide is typically formulated at a concentration of 0.1% in a cream, and hydrocortisone is typically formulated at a concentration of 1% or 2.5% in a cream. Certain topical corticosteroids, such as betamethasone dipropionate, clobetasol propionate, diflorasone diacetate, fluocinonide, and halobetazole propionate, are considered to be highly potent. Certain topical corticosteroids, such as amcinonides, desoximethasone, halcinonide, and triamcinolone acetonide, are considered to be highly potent. For example, certain topical corticosteroids such as betamethasone valerate, crocortrullone pivalate, fluocinolone acetonide, flulandrenolide, fluocinonide, fluticasone propionate, hydrocortisone butyrate, hydrocortisone valerate, mometasone furoate, and prednicarbate are considered to have moderate potency. For example, certain topical corticosteroids such as alclometasone dipropionate, desonide, and hydrocortisone are considered to have low potency. TCS can be applied to the affected area once daily, twice daily, three times daily, or as needed. In some embodiments, the patient is poorly controlled by topical corticosteroids. In some embodiments, the topical corticosteroid is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone. In some embodiments, the topical corticosteroid is administered simultaneously with or consecutively with an anti-IL-13 antibody. In some embodiments, topical corticosteroids are administered concurrently with anti-IL-13 antibodies.

[0059] When used herein, the terms “a,” “an,” “the,” and similar terms as used in the context of this disclosure (particularly in the context of the claims) should be construed to encompass both singular and plural forms unless otherwise specified or unless the context clearly contradicts this.

[0060] When used herein, the term "approximately" means a figure that is sufficiently close to the stated figure, for example, within ±10% of the stated figure.

[0061] As used herein, the term “antibody” refers to an immunoglobulin molecule that binds to an antigen. Embodiments of an antibody include monoclonal antibodies, polyclonal antibodies, human antibodies, humanized antibodies, chimeric antibodies, or conjugate antibodies. Antibodies may be of any class (e.g., IgG, IgE, IgM, IgD, IgA) and any subclass (e.g., IgG1, IgG2, IgG3, IgG4).

[0062] An exemplary antibody is an immunoglobulin G (IgG) type antibody composed of four polypeptide chains: two heavy chains (HC) and two light chains (LC) crosslinked via interchain disulfide bonds. The amino-terminal portion of each of the four polypeptide chains contains a variable region of approximately 100 to 125 or more amino acids, primarily involved in antigen recognition. The carboxy-terminal portion of each of the four polypeptide chains contains a constant region, primarily involved in 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).

[0063] The VH and VL regions can be further subdivided into hypervariable regions called complementarity determining regions (CDRs), which contain scattered, more conserved regions called framework regions (FRs). CDRs are exposed on the surface of the protein and are important regions of the antibody for antigen-binding specificity. Each VH and VL consists of three CDRs and four FRs, arranged from the amino terminus to the carboxyl terminus in the order FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. Hereinafter, the three CDRs of the heavy chain are referred to as "HCDR1, HCDR2, and HCDR3," and the three CDRs of the light chain are referred to as "LCDR1, LCDR2, and LCDR3." CDRs contain the majority of the residues that form specific interactions with the antigen.The assignment of amino acid residues to CDRs is attributed to 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, 406, 228-256 (2011)), or IMGT (the international ImMunoGeneTics This can be done according to well-known schemes, including those described in the database available at www.imgt.org (Lefranc et al., Nucleic Acids Res. 1999;27:209-212).

[0064] Exemplary embodiments of the antibodies of this disclosure also include antibody fragments or antigen-binding fragments, which include at least a portion of an antibody that retains the ability to specifically interact with an antigen, such as Fab, Fab', F(ab')2, Fv fragment, scFv, scFab, disulfide-bound Fv(sdFv), Fd fragment, and linear antibodies.

[0065] As used herein, the terms “bind” and “binds” mean, unless otherwise specified, the ability of a protein or molecule to form a certain type of chemical bond or attractive interaction with another protein or molecule, resulting in close proximity between two proteins or molecules as determined by common methods known in the art.

[0066] As used herein, the term “flare” refers to an increase in signs and / or symptoms that result in a gradual increase in therapy, which may be due to an increase in dose, a switch to a higher potency class of drug, or the initiation of another drug.

[0067] As used herein, the term "high affinity" means approximately 10 -8 Less than M, for example, 10 -15 M~10 -8 M, or 10 -12 M~10 -9 The equilibrium dissociation constant (K) of M D This refers to the binding strength of antibodies to human IL-13 that possess the characteristic (IQ).

[0068] The term "human IL-13" refers to human interleukin-13 (also known as P600), an immunomodulatory cytokine primarily produced by activated Th2 cells. Two known human IL-13 isoforms exist: isoform a and isoform b. As used herein, the term "human IL-13" refers collectively to all human IL-13 isoforms. The amino acid sequence of human IL-13 isoform a can be found at NCBI acceptance number NP_002179.2. The amino acid sequence of human IL-13 isoform b can be found at NCBI acceptance number NP_001341922.1.

[0069] As used herein, the term “inadequate response” means the failure to achieve good disease control of atopic dermatitis after using the treatment for the period recommended by the product prescription information (e.g., failure to achieve IGA ≤ 2 or EASI-75), or the occurrence of a flare of atopic dermatitis during treatment.

[0070] As used herein, the terms “intolerance” or “intolerant” refer to unacceptable toxicity (e.g., elevated creatinine, elevated liver function test results, uncontrolled hypertension, paranesthesia, headache, nausea, hirsutism), or the need for a dose or duration of the drug exceeding the dose or duration specified in the prescribing information.

[0071] As used herein, the term "patient" refers to a human patient.

[0072] As used herein, the terms “topical corticosteroid” or “TCS” include topical corticosteroids of Group I, II, III, and IV. According to the World Health Organization’s Anatomical Therapeutic Chemical (ATC) Classification System, corticosteroids are classified into weak (Group I), moderately potent (Group II), potent (Group III), and very potent (Group IV) based on their activity compared to hydrocortisone. Group IV TCS (very potent) are up to 600 times potent than hydrocortisone and include clobetasol and halcinonide. Group III TCS (potent) are 50 to 100 times potent than hydrocortisone and include, but are not limited to, betamethasone valerate, betamethasone dipropionate, diflucortolone valerate, hydrocortisone-17-butyrate, mometasone furoate, and methylprednisolone aceponate. Group II TCSs (moderately potent) are 2 to 25 times potent than hydrocortisone and include, but are not limited to, clobetazone butyrate and triamcinolone acetonide. Group I TCSs (weak or mild) include hydrocortisone, prednisolone, and methylprednisolone.

[0073] As used herein, “treatment” or “to treat” means all processes that may slow, control, delay, or halt the progression of a disorder or disease disclosed herein, or improve the symptoms of the disorder or disease, but not necessarily imply the complete elimination of all symptoms of the disorder or disease. Treatment includes the administration of proteins, nucleic acids, vectors, or compositions for the treatment of a patient, in particular a disease or condition in a human. [Examples]

[0074] Example 1. A randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of leburikizumab in combination with topical corticosteroids in adult and adolescent patients with moderate to severe atopic dermatitis that is not adequately controlled with cyclosporine or for which cyclosporine is not medically recommended.

[0075] This is a randomized, double-blind, placebo-controlled, parallel-group study with a duration of 72 weeks (up to 4 weeks of screening, 52 weeks of treatment [with the final dose administered at week 50], and 18 weeks of post-final dose safety follow-up). The study is designed to confirm the efficacy and safety of leburikizumab administered concurrently with TCS in adolescents and adults with moderate to severe Alzheimer's disease that is not adequately controlled with cyclosporine or for which cyclosporine is not medically recommended.

[0076] The study consists of two treatment periods: a 16-week double-blind treatment period (or induction period), followed by a 36-week open-label maintenance period. The study is double-blind until week 18, and then open-label from week 20 onward. Patients who received placebo during the initial treatment period (or induction period) will receive a loading dose of leburikizumab at weeks 16 and 18. To maintain blinding at weeks 16 and 18, all patients will receive two injections at these times (either two injections of leburikizumab or one injection of leburikizumab and one injection of placebo). From week 20 onward, all patients will receive one injection of leburikizumab 250 mg Q2W.

[0077] the purpose: This study is designed to evaluate the efficacy and safety of leburikizumab in combination with TCS up to week 52 in adults and adolescents (ages 12 to under 18, weight ≥ 40 kg) with moderate to severe Alzheimer's disease (AD) that is not adequately controlled with cyclosporine or for which cyclosporine is not medically recommended.

[0078] The primary objective is to evaluate the efficacy of lebrikizumab compared to placebo in patients who are not adequately controlled with cyclosporine or for whom cyclosporine is not medically recommended, up to a maximum of 16 weeks.

[0079] The second objectives include: (1) evaluating efficacy in patients who are not adequately controlled with cyclosporine or for whom cyclosporine is not medically recommended from weeks 16 to 52; (2) evaluating the safety and tolerability of leburikizumab in patients who are not adequately controlled with cyclosporine or for whom cyclosporine is not medically recommended up to week 16; and (3) evaluating the safety and tolerability of leburikizumab in patients who are not adequately controlled with cyclosporine or for whom cyclosporine is not medically recommended up to week 68.

[0080] The exploratory objectives are to identify biomarkers associated with clinical improvement that may be predictors of treatment response, and to explore biomarker modifications after treatment.

[0081] Patient population A sufficient number of patients will be screened, and approximately 312 patients with moderate to severe Alzheimer's disease (AD) will be randomized.

[0082] Inclusion Criteria: Patients eligible for inclusion in this study must meet all of the following criteria. 1. Adults and young people (12 years old or older, under 18 years old, weighing 40 kg or more). 2. Chronic Alzheimer's disease (according to Hanifin and Rajka criteria) was present more than one year prior to the screening visit. 3. The patient's EASI score at baseline visit is 16 or higher. 4. The IGA score at baseline visit is 3 or higher (moderate) (on a scale of 0 [none] to 4 [severe]). 5. The body surface area (BSA) associated with atopic dermatitis (AD) at baseline visit is 10% or more. 6. A physician-recorded medical history of inadequate response to existing topical medications within six months prior to screening, defined as failure to achieve good disease control (e.g., failure to achieve IGA ≤ 2) after using a moderate-potency TCS for at least four weeks, or for the maximum period recommended by the product prescribing information (e.g., 14 days for high / very high-potency TCS) (whichever is shorter). 7. Medical history recorded by the following physicians: (a) No prior CsA exposure, i. Medical contraindications (e.g., uncontrolled hypertension while taking medication), or ii. Use of prohibited concomitant medications (e.g., statins, digoxin, macrolide antibiotics, barbiturates, anticonvulsants, nonsteroidal anti-inflammatory drugs, diuretics, angiotensin-converting enzyme inhibitors, St. John's wort), or iii. Increased susceptibility to CsA-induced renal impairment (elevated creatinine) and / or liver injury (elevated functional tests), or iv. Increased risk of serious infection, or v. Hypersensitivity to CsA active substances or excipients; therefore, is this not currently a candidate for CsA treatment? (b) Or previously exposed to CsA and treated for CsA, i. Intolerance and / or unacceptable toxicity (e.g., elevated creatinine, elevated liver function tests, uncontrolled hypertension, paresthesia, headache, nausea, hirsutism), or ii. The need for or response to CsA at a dose or duration exceeding that specified in the prescribing information is insufficient, and therefore treatment should not be continued or resumed. 8. Participants completed an electronic diary (eDiary) documenting itching and sleep deprivation for at least four days within the seven days prior to randomization. 9. I am willing and able to follow all clinical visit and research-related procedures and questionnaires. 10. Continue abstinence or use effective contraception during the study and for at least 18 weeks after the last dose of lebrikizumab or placebo. 11. The patient must provide signed informed consent.

[0083] Exclusion Criteria: Patients who meet any of the following criteria are not eligible for inclusion in this study. 1. Previous participation in a leburikizumab clinical study. 2. Treatment with IL-4 or IL-13 antagonist biological therapy prior to baseline visit. Exception: Prior treatment with dupilumab is acceptable in a subset of patients. A washout of at least 8 weeks prior to baseline visit is required for this subpopulation. 3. Treatment with topical corticosteroids within one week prior to baseline visit. 4. Treatment with a topical calcineurin inhibitor such as crisabolol or a cannabinoid, or a phosphodiesterase-4 inhibitor, within two weeks prior to baseline visit. 5. Treatment with any of the following medications within 4 weeks prior to baseline visit: a. Immunosuppressive / immunomodulatory drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate mofetil, interferon-γ, JAK inhibitors, azathioprine, methotrexate). b. Phototherapy and photochemotherapy (PUVA) for Alzheimer's disease (AD). 6. Treatments received prior to baseline visit: a. The investigational drug, whichever is longer: within 8 weeks or within 5 half-lives (if known). b. B-cell depletion biological agents containing but not limited to rituximab, administered within the last 6 months. c. Another biologic product with a half-life of 16 weeks or less, or 5 half-lives (if known), whichever is longer. 7. Treatment with a live (attenuated) vaccine within 12 weeks of the baseline visit planned during the study, or 18 weeks after discontinuation of the study treatment. 8. A history of anaphylaxis as defined by the Sampson criteria. 9. Regular use of tanning booths / parlors within four weeks of a screening visit (more than two visits per week). 10. Uncontrolled chronic conditions that may require a burst of oral corticosteroids, such as comorbid severe uncontrolled asthma (defined as an ACQ-5 score of 1.5 or higher, or a history of two or more asthma exacerbations in the past 12 months requiring systemic [oral and / or parenteral] corticosteroid treatment or hospitalization for more than 24 hours). 11. You had had any of the following types of infections within three months of screening, or you developed any of these infections before randomization: a. Severe (requiring hospitalization and / or intravenous or equivalent oral antibiotic treatment), b. Opportunistic (as defined in Winthrop et al. 2015). Note: Herpes zoster is considered active and ongoing until all vesicles have dried and formed a crust. c. Chronic (symptoms, signs, and / or duration of treatment for 6 weeks or more), d. Recurrent (including, but not limited to, herpes simplex, herpes zoster, recurrent cellulitis, and chronic osteomyelitis). 12. Currently, you have an infection with hepatitis B virus (HBV), or you have a chronic infection with it. 13. Currently infected with hepatitis C virus (HCV) (i.e., HCV RNA positive). 14. The patient has a known history of cirrhosis and / or chronic hepatitis of any etiology. 15. Diagnosed with an active endoparasitic infection or at high risk of such infection. 16. A history of known or suspected immunosuppression, including a history of invasive opportunistic infections despite remission of infection (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystisosis, and aspergillosis), or an unusually frequent, recurrent, or prolonged infection as determined by the principal investigator. 17. History of human immunodeficiency virus (HIV) infection or positive HIV serology at the time of screening. 18. Any clinically significant test result from chemical, blood, or urine tests obtained at the screening visit, in the opinion of the principal investigator. 19. The presence of skin comorbidities that may interfere with research evaluation. 20. History of malignant tumors, including mycosis fungoides, within the five years prior to the screening visit. Excluding completely treated cervical carcinoma in situ, completely treated and resolved non-metastatic squamous cell carcinoma or basal cell carcinoma of the skin, with no evidence of recurrence in the past 12 weeks. 21. Severe comorbidities that, in the opinion of the Principal Investigator, would adversely affect a patient's participation in the study. Any other medical or psychological conditions that, in the opinion of the Principal Investigator, could suggest a new disease and / or a disease that is not well understood, could pose an undue risk to the patient for participation in this clinical trial, make patient participation unreliable, or interfere with the evaluation of the study. 22. Pregnant or breastfeeding women, or women who are expected to become pregnant or breastfeed during the study. 23. It had significant adverse effects on TCS (e.g., intolerance to treatment, hypersensitivity reactions, marked skin atrophy, and systemic effects) that would be assessed by the principal investigator or treating physician and would prevent further use.

[0084] Exclusion criteria include prior treatment with certain medications that require a washout period before the start of the trial (see Table 3).

[0085] Table 3. Exclusion of previous treatments and washout periods [Table 3]

[0086] Research drugs: The pharmaceutical composition containing 125 mg / mL of lebrikizumab or placebo is supplied as a sterile, pre-filled syringe equipped with a pre-assembled needle safety device (PFS-NSD) for subcutaneous administration to the patient. The lebrikizumab sequence is shown in Table 1. The placebo solution is identical in appearance and volume to the active solution, except that it does not contain lebrikizumab.

[0087] Research design: The study consists of two treatment periods: a 16-week double-blind initial treatment period (or induction period), followed by a 36-week open-label maintenance period (see Figure 1). The study is double-blinded until week 18, and then becomes open-label from week 20 onward.

[0088] During a 16-week induction period, approximately 312 patients will be randomized in a 2:1 ratio to receive either 250 mg of lebrikizumab via SC injection Q2W (once every two weeks) (with a 500 mg loading dose given at baseline (week 0) and week 2) or placebo. Randomization will be stratified by prior dupilumab use, age (adolescent patients aged 12 to under 18 years constitute up to 12.5% ​​of the total population compared to adults aged 18 years and older), and baseline disease severity (IGA 3 to 4).

[0089] All enrolled patients are required to initiate treatment with a moderate- or low-potency TCS at baseline and continue it throughout the study. A moderate-potency TCS, e.g., triamcinolone acetonide 0.1% cream, and a mild TCS, e.g., hydrocortisone 1% cream (for use in sensitive skin areas), will be provided for use concurrently with levukizumab in this clinical trial.

[0090] After completing the 16-week induction period, patients enter the maintenance period. Patients who received leburikizumab 250 mg Q2W during the induction period will continue to receive leburikizumab 250 mg Q2W during the maintenance period.

[0091] Patients who received placebo during the induction period will receive the following loading doses of leburikizumab: 500 mg of leburikizumab at weeks 16 and 18. Blinding will be maintained at weeks 16 and 18 to allow placebo patients to receive these leburikizumab loading doses during the maintenance period. Therefore, the study will be open-label from week 20 onward. Patients who received placebo during the induction period will receive 250 mg of leburikizumab Q2W from week 20 onward during the maintenance period.

[0092] Responses will be reassessed along the maintenance period. Patients who do not achieve EASI50 after at least two consecutive visits assessed at weeks 24, 28, 32, 36, 40, 44, or 48 will be discontinued from the study.

[0093] Evaluation items The primary objective of this study is to evaluate the efficacy of lebrikizumab compared to placebo in patients who are not adequately controlled with cyclosporine or for whom cyclosporine is not medically recommended, up to 16 weeks. Efficacy will be measured using the following criteria: (i) clinical signs: EASI, IGA, BSA with AD lesions; (ii) clinical signs and patient-reported symptoms: SCORAD; (iii) symptoms reported by AD patients: pruritus NRS, sleep insomnia scale, skin pain NRS, POEM; (iv) quality of life (QoL) and disease impact: one or more of the following: DLQI or CDLQI, DLQI-R, WHO-5, RECAP, and TSQM-9.

[0094] The primary endpoint of the study is the percentage of patients achieving EASI75 (a reduction of 75% or more from baseline in the EASI score) at week 16. Secondary endpoints include the percentage of patients achieving EASI90 at week 16, the percentage of patients achieving IGA 0 / 1 and 2-point improvement at week 16, the percentage of patients achieving a 4-point improvement in pruritus NRS at week 16, the percentage of patients achieving EASI90 at week 16, the percentage of patients achieving EASI75, EASI90, and EASI50 (up to week 16 visit), the change from baseline BSA up to week 16 visit, the change from baseline SCORAD up to week 16 visit, the change from baseline pruritus NRS up to week 16 visit, and the baseline up to week 16 visit. This includes changes from sleep deprivation, changes from baseline POEM up to week 16 visit, changes from baseline DLQI / CDLQI up to week 16 visit, percentage of patients achieving a 4-point improvement in DLQI / CDLQI up to week 16 visit, percentage of days without TCS from baseline up to week 16 visit, time (days) to TCS-free up to week 16 visit, changes from baseline skin pain NRS up to week 16 visit, and percentage of patients achieving a 4-point improvement in skin pain NRS at week 16. Other exploratory endpoints include changes from baseline RECAP by week 16 visit, changes from baseline WHO-5 up to week 16 visit, TSQM-9 up to week 16 visit, changes from baseline DLQI-R up to week 16 visit, and time to EASI50, EASI75, and EASI90 (days) up to week 16 visit.

[0095] The second objective is to evaluate the efficacy in patients who are not adequately controlled with cyclosporine or for whom cyclosporine is not medically recommended, from week 16 to a maximum of week 52. The endpoints for this second objective are the percentage of patients who maintain an EASI-75 at week 52 and achieve an EASI-75 at week 16, the percentage of patients who achieve EASI75, EASI90, or EASI50 (between week 16 and week 52 visits), and IGA. Percentage of patients achieving 0 / 1 and 2-point improvement (between week 16 and week 52 visits), percentage of patients achieving a 4-point improvement in pruritus NRS (between week 16 and week 52 visits), change from baseline BSA (between week 16 and week 52 visits), change from baseline SCORAD (between week 16 and week 52 visits), change from baseline pruritus NRS (between week 16 and week 52 visits), change from baseline sleep deprivation (between week 16 and week 52 visits), change from baseline POEM (between week 16 and week 52 visits) This includes changes (up to the visit), changes from baseline DLQI / CDLQI (from week 16 to week 52), the percentage of patients achieving a 4-point improvement in DLQI / CDLQI (from week 16 to week 52), the percentage of days without TCS from baseline (from week 16 to week 52), time to TCS-free (in days), changes from baseline skin pain NRS (from week 16 to week 52), and the percentage of patients achieving a 4-point improvement in skin pain NRS (from week 16 to week 52). Other exploratory endpoints include change from baseline RECAP (from week 16 to week 52 visit), change from baseline WHO-5 (from week 16 to week 52 visit), TSQM-9 (from week 16 to week 52 visit), change from baseline DLQI-R (from week 16 to week 52 visit), and time to EASI75 and EASI90 (days) (from week 16 to week 52 visit).

[0096] To evaluate the safety and tolerability of levukizumab in patients who are not adequately controlled with cyclosporine or for whom cyclosporine is not medically recommended, the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), related TEAEs, related SAEs, TEAEs leading to discontinuation of the study treatment, adverse events of special interest (AESIs) (e.g., conjunctivitis, herpes infection, or herpes zoster), and adverse events (AEs), including death, will be monitored and evaluated. Blood and urine samples will be collected from each patient and subjected to clinical tests such as blood chemistry, hematology, serology, coagulation, and urinalysis, with results and changes from baseline recorded and evaluated. A complete physical examination will be performed, including evaluation of at least the cardiovascular, respiratory, gastrointestinal, and nervous systems, and any abnormalities in the physical examination will be recorded and evaluated. Vital signs, such as systolic and diastolic blood pressure (mmHg), heart rate (beats per minute), respiratory rate (respiratory rate per minute), and body temperature (°C), are measured, and the results and changes from baseline are recorded and evaluated.

[0097] The exploratory objectives are to identify biomarkers associated with clinical improvement that may be predictors of treatment response, and to explore biomarker modifications after treatment. Blood samples will be collected from patients and subjected to transcriptome, genomic, and protein analyses. Further associations with EASI outcomes will be investigated.

[0098] Statistical analysis will be performed on the primary and secondary outcome measures.

Claims

1. A method for treating moderate to severe atopic dermatitis or reducing itching associated with atopic dermatitis in a patient, comprising administering to the patient a pharmaceutical composition containing an antibody that binds to human IL-13, The patient has shown an insufficient response to or intolerance of cyclosporine, or cyclosporine is not medically recommended for the patient. A method wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 containing SEQ ID NO: 1, HCDR2 containing SEQ ID NO: 2, and HCDR3 containing SEQ ID NO: 3, and the VL comprises LCDR1 containing SEQ ID NO: 4, LCDR2 containing SEQ ID NO: 5, and LCDR3 containing SEQ ID NO:

6.

2. A method for treating moderate to severe atopic dermatitis, or for reducing itching associated with atopic dermatitis, The selection of patients who have moderate to severe atopic dermatitis and have shown an insufficient response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended, The process includes administering a pharmaceutical composition containing an antibody that binds to human IL-13 to the patient, A method wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 containing SEQ ID NO: 1, HCDR2 containing SEQ ID NO: 2, and HCDR3 containing SEQ ID NO: 3, and the VL comprises LCDR1 containing SEQ ID NO: 4, LCDR2 containing SEQ ID NO: 5, and LCDR3 containing SEQ ID NO:

6.

3. The method according to claim 1 or 2, wherein the patient has moderate to severe atopic dermatitis for at least one year.

4. The method according to any one of claims 1 to 3, wherein the moderate to severe atopic dermatitis is determined by the Hanifin and Rajka criteria.

5. The method according to any one of claims 1 to 3, wherein the moderate to severe atopic dermatitis is determined by the Rajka and Langerand criteria.

6. The method according to any one of claims 1 to 5, wherein the patient has an eczema area and severity index (EASI) score of 16 or more, an investigator's global assessment (IGA) score of 3 or more, and a body surface area (BSA) affected by atopic dermatitis of more than 10% prior to administration of the pharmaceutical composition.

7. The method according to any one of claims 1 to 6, wherein the patient showed an insufficient response to topical corticosteroids.

8. The method according to any one of claims 1 to 7, wherein the patient is 12 years of age or older.

9. A method for treating moderate to severe atopic dermatitis, or for reducing itching associated with atopic dermatitis, i. Being 12 years of age or older ii. Having chronic atopic dermatitis for more than one year according to the Hanifin and Rajka criteria, iii. Having an EASI score of 16 or higher, iv. Having an IGA score of 3 or higher, v. Having more than 10% of the body surface area affected by atopic dermatitis, vi. Patients who showed an insufficient response to topical corticosteroids, and vii. Selecting patients who have shown an inadequate response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended, The process includes administering a pharmaceutical composition containing an antibody that binds to human IL-13 to the patient, A method wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 containing SEQ ID NO: 1, HCDR2 containing SEQ ID NO: 2, and HCDR3 containing SEQ ID NO: 3, and the VL comprises LCDR1 containing SEQ ID NO: 4, LCDR2 containing SEQ ID NO: 5, and LCDR3 containing SEQ ID NO:

6.

10. The method according to any one of claims 1 to 9, wherein the cyclosporine is cyclosporine A.

11. The method according to any one of claims 1 to 10, wherein the patient showed an insufficient response to cyclosporine.

12. The method according to claim 11, wherein the patient showed an insufficient response to cyclosporine at least four weeks prior to administration of the pharmaceutical composition.

13. The method according to any one of claims 1 to 10, wherein the patient exhibited intolerance to cyclosporine.

14. Cyclosporine is used for the following reasons: i. medical contraindications, ii. Use of prohibited concomitant medications. iii. Increased susceptibility to cyclosporine-induced renal and / or hepatic injury. iv. Increased risk of serious infection, or v. The method according to any one of claims 1 to 10, which is not medically recommended for the patient due to one of the following conditions: hypersensitivity to the cyclosporine active substance or excipient.

15. The method according to any one of claims 1 to 14, wherein the patient showed an insufficient response to a topical corticosteroid at least two weeks prior to administration of the pharmaceutical composition.

16. The method according to any one of claims 1 to 15, wherein the patient has not been previously exposed to dupilumab.

17. The method according to any one of claims 1 to 15, wherein the patient has been previously exposed to dupilumab.

18. The method according to any one of claims 1 to 17, wherein the antibody comprises VH containing SEQ ID NO: 7 and VL containing SEQ ID NO:

8.

19. The method according to any one of claims 1 to 18, wherein the antibody comprises a heavy chain containing SEQ ID NO: 9 and a light chain containing SEQ ID NO:

10.

20. The method according to any one of claims 1 to 19, wherein the antibody is leburikizumab.

21. The method according to any one of claims 1 to 20, wherein the pharmaceutical composition comprises 250 mg or 500 mg of the antibody.

22. The method according to any one of claims 1 to 21, wherein the pharmaceutical composition is administered subcutaneously to the patient.

23. The method according to any one of claims 1 to 22, wherein the pharmaceutical composition is administered subcutaneously to the patient once every two weeks.

24. The method according to any one of claims 1 to 23, wherein the patient is treated with the pharmaceutical composition over a period of 16 to 52 weeks.

25. The method according to any one of claims 1 to 24, wherein the patient is treated with the pharmaceutical composition over a treatment period of 16 weeks.

26. The method according to claim 25, wherein during the treatment period, the patient is treated with a loading dose of the pharmaceutical composition containing 500 mg of the antibody in two doses, once every two weeks, and then treated with a subsequent dose of the pharmaceutical composition containing 250 mg of the antibody in seven doses, once every two weeks.

27. The method according to claim 25 or 26, further comprising determining the patient's EASI score after the treatment period.

28. The method according to claim 27, wherein the EASI score determined after the treatment period is reduced by 50% or more compared to the EASI score determined before administration of the first loading dose of the antibody.

29. The method according to claim 27, wherein the EASI score determined after the treatment period is reduced by 75% or more compared to the EASI score determined before administration of the first loading dose of the antibody.

30. The method according to claim 27, wherein the EASI score determined after the treatment period is reduced by 90% or more compared to the EASI score determined before administration of the first loading dose of the antibody.

31. The method according to any one of claims 25 to 30, further comprising determining the patient's IGA score after the treatment period.

32. The method according to claim 31, wherein the IGA score determined after the treatment period is 0 or 1, and the IGA score determined after the treatment period is reduced by 2 points or more compared to the IGA score determined before administration of the first loading dose of the antibody.

33. The method according to any one of claims 25 to 32, further comprising determining the percentage of BSAs in the patient that have developed atopic dermatitis after the treatment period.

34. The method according to any one of claims 25 to 33, further comprising determining the patient's Numerical Rating Scale (NRS) score after the treatment period.

35. The method according to claim 34, wherein the pruritus NRS score determined after the treatment period is reduced by 4 points or more compared to the pruritus NRS score determined before administration of the first loading dose of the antibody.

36. After the aforementioned treatment period, the following characteristics of the patient: i. Severity assessment method for atopic dermatitis (SCORAD), ii. sleep deprivation scale, iii. Skin pain NRS score, iv. Patient-assigned total score on the Eczema Scale (POEM), v. Dermatological Quality of Life Index (DLQI) score, Pediatric Dermatological Quality of Life Index (CDLQI), or DLQI-related (DLQI-R) score, vi. World Health Organization-5 Wellbeing Index (WHO-5) score, vii. Recap score for atopic eczema, viiii. The method according to any one of claims 25 to 35, further comprising determining one or more of the 9-item Treatment Satisfaction Questionnaire for Pharmacotherapy (TSQM-9) score.

37. The method according to any one of claims 25 to 36, wherein the patient is further treated with the pharmaceutical composition for a maintenance period of up to 36 weeks.

38. The method according to claim 37, wherein the patient is treated once every two weeks during the maintenance period with a maintenance dose of the pharmaceutical composition containing 250 mg of the antibody.

39. The method according to claim 37 or 38, further comprising determining the patient's EASI score during or after the maintenance period.

40. The method according to claim 39, wherein the EASI score determined during or after the maintenance period is reduced by 50% or more compared to the EASI score determined after the treatment period.

41. The method according to claim 39, wherein the EASI score determined during or after the maintenance period is reduced by 75% or more compared to the EASI score determined after the treatment period.

42. The method according to claim 39, wherein the EASI score determined during or after the maintenance period is reduced by 90% or more compared to the EASI score determined after the treatment period.

43. The method according to any one of claims 37 to 42, further comprising determining the patient's IGA score during or after the maintenance period.

44. The method according to claim 43, wherein the IGA score determined during or after the maintenance period is 0 or 1, and the IGA score determined during or after the maintenance period is reduced by 2 points or more compared to the IGA score determined after the treatment period.

45. The method according to any one of claims 37 to 44, further comprising determining the percentage of BSAs in the patient who developed atopic dermatitis during or after the maintenance period.

46. The method according to any one of claims 37 to 45, further comprising determining the patient's pruritus NRS score during or after the maintenance period.

47. The method according to claim 46, wherein the pruritus NRS score determined during or after the maintenance period is reduced by 4 points or more compared to the pruritus NRS score determined after the treatment period.

48. After the maintenance period, the following characteristics of the patient: i. SCORAD, ii. sleep deprivation scale, iii. Skin pain NRS score, iv. POEM total score, v. DLQI score, CDLQI, or DLQI-R score, vi. WHO-5 score, vii. RECAP score, viiii. The method according to any one of claims 37 to 47, further comprising determining one or more of the TSQM-9 scores.

49. The method according to any one of claims 1 to 48, wherein the pharmaceutical composition is administered to the patient using a subcutaneous administration device.

50. The method according to claim 49, wherein the subcutaneous administration device is selected from a pre-filled syringe, a disposable pen-type injection device, a microneedle device, a microinfuser device, a needleless injection device, or an autoinjector device.

51. The method according to any one of claims 1 to 49, further comprising administering one or more topical corticosteroids to the patient.

52. The method according to claim 51, wherein the one or more topical corticosteroids are triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone.

53. The method according to claim 51 or 52, wherein one or more local corticosteroids are administered simultaneously with the antibody.

54. A pharmaceutical composition comprising an antibody that binds to human IL-13 for use in the treatment of moderate to severe atopic dermatitis or the reduction of pruritus associated with atopic dermatitis in patients who have shown an insufficient response to or intolerance to cyclosporine, or for whom cyclosporine is not medically recommended, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 comprising SEQ ID NO: 1, HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3, and the VL comprising LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO: 5, and LCDR3 comprising SEQ ID NO:

6.

55. The aforementioned patient, i. Being 12 years of age or older ii. Having chronic atopic dermatitis for more than one year according to the Hanifin and Rajka criteria, iii. Having an EASI score of 16 or higher, iv. Having an IGA score of 3 or higher, v. More than 10% of BSA suffer from atopic dermatitis. vi. Patients who showed an insufficient response to topical corticosteroids, and vii. A pharmaceutical composition for use according to claim 54, wherein the patient has shown an insufficient response to or intolerance to cyclosporine, or cyclosporine is not medically recommended for the patient.

56. The pharmaceutical composition for use according to claim 54 or 55, wherein the pharmaceutical composition is for administration in combination with one or more topical corticosteroids.

57. Use of a pharmaceutical composition comprising an antibody conjugating to human IL-13 in the manufacture of a drug for the treatment of moderate to severe atopic dermatitis or for the reduction of pruritus associated with atopic dermatitis, in patients who have shown an insufficient response to or intolerance to cyclosporine or for whom cyclosporine is not medically recommended, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising HCDR1 comprising SEQ ID NO: 1, HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3, and the VL comprising LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO: 5, and LCDR3 comprising SEQ ID NO:

6.

58. The aforementioned patient, i. Being 12 years of age or older ii. Having chronic atopic dermatitis for more than one year according to the Hanifin and Rajka criteria, iii. Having an EASI score of 16 or higher, iv. Having an IGA score of 3 or higher, v. More than 10% of BSA suffer from atopic dermatitis. vi. Patients who showed an insufficient response to topical corticosteroids, and vii. The use according to claim 57, in which the patient has shown an insufficient response to or intolerance to cyclosporine, or in which cyclosporine is not medically recommended for the patient.

59. The use according to claim 57 or 58, wherein the pharmaceutical composition is intended for administration in combination with one or more topical corticosteroids.

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