Evaluation of the Effectiveness and Safety of Immunosuppressive and Biological Therapy of Atopic Dermatitis in Childhood

Study Overview
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Brief Summary
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This comparative study analyzes the efficacy and safety of treatment of children from 6 years of age suffering from moderate to severe atopic dermatitis using an inhibitor of IL4, IL13 and classical immunosuppressants.

Detailed Description
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This is a prospective study aimed at direct comparative analysis of the efficacy and safety of treatment of children from 6 years of age suffering from moderate and severe atopic dermatitis using a genetically engineered biological drug and classical immunosuppressants. Based on clinical and anamnestic data, compliance with the inclusion / exclusion criteria, the study included 160 patients from 6 years old, with moderate / severe atopic dermatitis. The initial indices were assessed: SCORAD- Scoring of Atopic Dermatitis (index for assessing the severity of atopic dermatitis); NRS- numeric rating scale for itch; CDLQI - The Children's Dermatology Life Quality Index; POEM- Patient-Oriented Eczema Measure (personalized assessment of eczema) and laboratory parameters: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, total bilirubin, direct bilirubin, serum albumin, blood urea specific IgE to food and household allergens, indicators of a clinical blood test, indicators of a general analysis of urine, indicators of a biochemical analysis of urine (creatinine, urea). In the presence of concomitant allergic pathology (bronchial asthma, allergic rhinitis), the CSMS [Combined Symptom and Medication Score] were additionally assessed (Scale for assessing nasal symptoms of rhinitis, taking into account the need for medication); VAS - Visual Analog Scale (visual analog scale); ACT- Asthma Control Test. Subsequently, systemic therapy was prescribed: metorexat (40 people), mycophenolate mofetil (40 people), cyclosporine (40 people) dupilumab (40 people).

Official Title
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Evaluation of the Effectiveness and Safety of Immunosuppressive and Biological Therapy of Atopic Dermatitis in Childhood

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Methotrexate therapy
* Drug: Mycophenolate mofetil therapy
* Drug: Cyclosporine therapy
* Drug: Dupilumab therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 6 years inclusive; Atopic dermatitis diagnosed at least 12 months before the start of the study; Atopic dermatitis of moderate or severe course; Consent to discontinue the use of the following prohibited drugs or any of the following therapies at least 4 weeks before the start of the study and not to use them throughout the study, unless otherwise specified below: Oral systemic corticosteroids; Other systemic immunosuppressive drugs; Phototherapy, including therapeutic phototherapy (psoralen plus ultraviolet A, ultraviolet B), excimer laser, and self-medication using a tanning bed; A signed and dated informed consent received from the patient's parents (guardians), as well as from a patient over 14 years of age, to participate in the study. Ability to attend control visits within the specified time frame Exclusion Criteria: Use of other genetically engineered biological preparations in therapy; Participation in other clinical trials; The presence of other concomitant skin diseases in the present or in the past, which could affect the assessment of the effect of the study drugs on the course of atopic dermatitis; The presence of herpetic eczema within 12 months before the start of the study; A history of two or more cases of herpetic eczema; The presence in the present of a skin infection for which is required or is being treated with antibiotics for topical use or systemic antibiotics; Therapy with the following drugs: Other genetically engineered biological preparations less than 5 half-lives before the start of the study. Any corticosteroid for oral and parenteral administration and administration, which were in therapy for 2 weeks before enrollment in the study, or the possible need for parenteral injection of corticosteroids during the course of the study. Intra-articular corticosteroid injection within 2 weeks prior to study enrollment; Note: The use of intranasal or inhaled steroids is permitted throughout the study. Extensive or complete disability, significantly limiting personal care or determining the inability to carry it out. Immunodeficiency disease; The presence in the past or present of any serious and / or unstable disease, which, in the opinion of the investigator, may pose an unacceptable risk to the patient in the case of the use of the investigational drug or interfere with the interpretation of the data; History of lymphoproliferative disease; or manifestations or symptoms suggesting the possible presence of lymphoproliferative disease, including lymphadenopathy or splenomegaly; either primary or recurrent malignant disease in active form; or remission after a clinically significant malignant disease lasting less than 5 years; The course of a viral, bacterial, fungal or parasitic infection; Failure or unwillingness of the patient or patient's parent / caregiver / patient legal guardian to comply with the requirements of research participants throughout the study and / or unwillingness to follow research restrictions / procedures, including the use of data loggers. Contraindications to the use of adrenaline.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group №1: Methotrexate therapy<br> | Drug: Methotrexate therapy<br>* Methotrexate subcutaneously 10-15 mg/m2 once every 7 days within 12 months<br>|
| Experimental: Group №2: Mycophenolate mofetil therapy<br> | Drug: Mycophenolate mofetil therapy<br>* Mycophenolate mofetil per os 500-700 mg/m2 2 times a day within 12 months<br>|
| Experimental: Group №3: Cyclosporine therapy<br> | Drug: Cyclosporine therapy<br>* Cyclosporine per os 3 mg/m2 2 times a day within 12 months<br>|
| Experimental: Group №4: Dupilumab therapy<br> | Drug: Dupilumab therapy<br>* Patients weighing <30 kg received an initial dose of 600 mg (2 injections of 300 mg subcutaneously), then 300 mg every 4 weeks. Patients weighing 30 to <60 kg received an initial dose of 400 mg (2 injections of 200 mg subcutaneously), then 200 mg every 2 weeks; Patients weighing 60 kg or more, the initial dose is 600 mg (2 injections of 300 mg subcutaneously), then 300 mg every 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SCORAD (Scoring of Atopic Dermatitis) | change of the SCORAD index | screening (baseline), 3, 4, 6 and 12 months from the start of therapy | 
| NRS (Numeric rating scale for itch) | change of the NRS | screening (baseline), 3, 4, 6 and 12 months from the start of therapy | 
| Adverse events | Adverse events monitoring | screening (baseline), 3, 4, 6 and 12 months from the start of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CDLQI (The Children's Dermatology Life Quality Index) | change of the CDLQI | screening (baseline), 3, 4, 6 and 12 months from the start of therapy | 
| POEM (Patient-Oriented Eczema Measure) | change of the POEM | screening (baseline), 3, 4, 6 and 12 months from the start of therapy | 
| CSMS (Combined Symptom and Medication Score) | change of the CSMS | screening (baseline), 3, 4, 6 and 12 months from the start of therapy | 
| VAS (Visual Analog Scale) | change of the VAS | screening (baseline), 3, 4, 6 and 12 months from the start of therapy | 
| ACT (Asthma Control Test) | change of the ACT | screening (baseline), 3, 4, 6 and 12 months from the start of therapy | 
| Concentration in the biochemical blood test of total IgE and specific IgE for food and household allergens | change in the Concentration in the biochemical blood test of total IgE, specific IgE-method ImmunoCap to food and household allergens | screening (baseline), 3, 4, 6 and 12 months from the start of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoids, Biologic Drugs, Methotrexate, Cyclosporine, dupilumab