A clinical trial evaluating the efficacy and safety of the drugs - cyclosporine and methotrexate in children and adolescents with moderate to severe atopic dermatitis.

INTERVENTION: Product Name: TACROLIMUS, Product Code:SUB10797MIG, Pharmaceutical Form: OINTMENT, Other descriptive name: , Strength: , Product Name: METHOTREXATE, Product Code:SUB08856MIG, Pharmaceutical Form: ORAL SOLUTION, Other descriptive name: , Strength: , Product Name: CICLOSPORIN, Product Code:SUB06250MIG, Pharmaceutical Form: ORAL LIQUID, Other descriptive name: , Strength: , Product Name: MOMETASONE FUROATE, Product Code:SUB03318MIG, Pharmaceutical Form: OINTMENT, Other descriptive name: , Strength: , Product Name: TACROLIMUS, Product Code:SUB10797MIG, Pharmaceutical Form: OINTMENT, Other descriptive name: , Strength: CONDITION: atopic dermatitis ; MedDRA version: 21.1Level: LLTClassification code: 10003639Term: Atopic dermatitis Class: 10040785 Therapeutic area: Diseases [C] ‐ Skin and Connective Tissue Diseases [C17] PRIMARY OUTCOME: Main Objective: The main objective of the study is to compare the efficacy and safety of cyclosporine and methotrexate in children and adolescent subjects with moderate‐to‐severe atopic dermatitis. Primary end point(s): Proportion of patients achieving 75% improvement in EASI (EASI75) from baseline at week 32. Secondary Objective: To assess the efficacy of MTX or CsA monotherapy compared to standard of care on skin lesions improvement and subjective parameters (itch and quality of sleep) and health‐related quality of life, To assess the safety and tolerability of MTX and CsA compared to standard of care., To assess the period of clinical remission after treatment cessation at week 32. INCLUSION CRITERIA: At the moment of giving written informed consent the patient must be between 2‐18 y.o., The participant, parent(s)/legal guardian(s) must be willing and give permission to use only one emollient during the clinical trial, provided by the Sponsor., The patient must be vaccinated according to national regulations, the last vaccination at least one month before the first dose of IMP (8 weeks in case of live vaccine). There are no contraindications to vaccination with live vaccines if the patient is in the standard of care arm and 12 weeks after the end of treatment in the arm with CsA and MTX., Diagnosis of moderate or severe AD established at least 6 months before baseline. Moderate‐to‐severe AD (EASI>16, BSA>10, SCORAD>25) must be confirmed based on clinical features on the screening and baseline visits., The patient, according to doctor’s opinion, is a candidate for systemic therapy., Body weight of the participant is within 3 and 97 percentile grid, matched for se SECONDARY OUTCOME: Secondary end point(s):Change in Children’s Dermatology Life Quality Inde X(CDLQI) score from baseline to Week 16. Secondary end point(s):Change in Children’s Dermatology Life Quality Inde X(CDLQI) score from baseline to Week 32 Secondary end point(s):Change in Family Dermatology Life Quality Inde X(FDQL) from baseline to week 16. Secondary end point(s):Change in Family Dermatology Life Quality Inde X(FDQL) from baseline to week 32. Secondary end point(s):Change in Infant’s Dermatitis Quality of Life (IDQI) from baseline to week 16. Secondary end point(s):Change in Infant’s Dermatitis Quality of Life (IDQI) from baseline to week 32. Secondary end point(s):Change in Patient‐Oriented Eczema Measure (POEM) from baseline to week 16. Secondary end point(s):Change in Patient‐Oriented Eczema Measure (POEM) from baseline to week 32. Secondary end point(s):Change in Scoring Atopic Dermatitis (SCORAD) from baseline to week 16 Secondary end point(s):Change in Scoring Atopic Dermatitis (SCORAD) from baseline to week 32. Secondary end point(s):Incidence of treatment‐emergent AE from baseline through week 16. Secondary end point(s):Incidence of treatment‐emergent AE from baseline through week 32. Secondary end point(s):Incidence of treatment‐emergent AE leading to treatment discontinuation from baseline through week 16. Secondary end point(s):Incidence of treatment‐emergent AE leading to treatment discontinuation from baseline through week 32. Secondary end point(s):Itch Reduction of Pruritus in numeric rating scale (NRS) and in VAS (visual analogue scale) from baseline to Week 16. Secondary end point(s):Itch Reduction of Pruritus in numeric rating scale (NRS) and in VAS (visual analogue scale) from baseline to Week 32. Secondary end point(s):Percent change in EASI score from baseline to week 16. Secondary end point(s):Percent change in EASI score from baseline to week 32. Secondary end point(s):Proportion of patients achieving 75% improvement in EASI (EASI75) from baseline at week 16. Secondary end point(s):Proportion of patients with Investigator’s Global Assessment (IGA) 0 (clear) or 1 (almost clear) at week 16. Secondary end point(s):Proportion of patients with Investigator’s Global Assessment (IGA) 0 (clear) or 1 (almost clear) at week 32. Secondary end point(s):Time to exacerbation of AD (loss of at least 50% of the EASI response at week 32) after treatment cessation at week 32.