A D Irvine1,2,3, A P Jones4, P Beattie5, S Baron6, F Browne2, F Ashoor4, L O'Neill7, A Rosala-Hallas4, T Sach8, C Spowart4, L Taams9, C Walker6, M Wan6, N Webb10, P Williamson4, C Flohr6. 1. Clinical Medicine, Trinity College Dublin, Dublin, Ireland. 2. Paediatric Dermatology, Our Lady's Children Hospital Crumlin, Dublin, Ireland. 3. National Children's Research Centre, Crumlin, Dublin, Ireland. 4. Clinical Trials Research Centre, Department of Biostatistics, University of Liverpool, Liverpool, U.K. 5. Royal Hospital for Children NHS Trust, Glasgow, U.K. 6. Unit for Population-Based Dermatology Research, St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, U.K. 7. Biochemistry, Trinity College Dublin, Dublin, Ireland. 8. Health Economics Group, Norwich Medical School, University of East Anglia, Norwich, U.K. 9. Centre for Molecular and Cellular Biology of Inflammation, King's College London, London, U.K. 10. Renal Research Laboratories, Manchester Royal Infirmary, Manchester, U.K.
Abstract
BACKGROUND:Oral systemic immunomodulatory medication is regularly used off-licence in children with severe atopic eczema. However, there is no firm evidence regarding the effectiveness, safety, cost-effectiveness and impact on quality of life from an adequately powered randomized controlled trial (RCT) using systemic medication in children. OBJECTIVES: To assess whether there is a difference in the speed of onset, effectiveness, side-effect profile and reduction in flares post-treatment between ciclosporin (CyA) and methotrexate (MTX), and also the cost-effectiveness of the drugs. Treatment impact on quality of life will also be examined in addition to whether FLG genotype influences treatment response. In addition, the trial studies the immune-metabolic effects of CyA and MTX. METHODS: Multicentre, parallel group, assessor-blind, pragmatic RCT of 36 weeks' duration with a 24-week follow-up period. In total, 102 children aged 2-16 years with moderate-to-severe atopic eczema, unresponsive to topical treatment will be randomized (1 : 1) to receive MTX (0·4 mg kg-1 per week) or CyA (4 mg kg-1 per day). RESULTS: The trial has two primary outcomes: change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare following treatment cessation. CONCLUSIONS: This trial addresses important therapeutic questions, highlighted in systematic reviews and treatment guidelines for atopic eczema. The trial design is pragmatic to reflect current clinical practice.
RCT Entities:
BACKGROUND: Oral systemic immunomodulatory medication is regularly used off-licence in children with severe atopic eczema. However, there is no firm evidence regarding the effectiveness, safety, cost-effectiveness and impact on quality of life from an adequately powered randomized controlled trial (RCT) using systemic medication in children. OBJECTIVES: To assess whether there is a difference in the speed of onset, effectiveness, side-effect profile and reduction in flares post-treatment between ciclosporin (CyA) and methotrexate (MTX), and also the cost-effectiveness of the drugs. Treatment impact on quality of life will also be examined in addition to whether FLG genotype influences treatment response. In addition, the trial studies the immune-metabolic effects of CyA and MTX. METHODS: Multicentre, parallel group, assessor-blind, pragmatic RCT of 36 weeks' duration with a 24-week follow-up period. In total, 102 children aged 2-16 years with moderate-to-severe atopic eczema, unresponsive to topical treatment will be randomized (1 : 1) to receive MTX (0·4 mg kg-1 per week) or CyA (4 mg kg-1 per day). RESULTS: The trial has two primary outcomes: change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare following treatment cessation. CONCLUSIONS: This trial addresses important therapeutic questions, highlighted in systematic reviews and treatment guidelines for atopic eczema. The trial design is pragmatic to reflect current clinical practice.