A randomized controlled trial protocol assessing the effectiveness, safety and cost‐effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children: the TREatment of severe Atopic eczema Trial (TREAT)

Background: Oral systemic immuno‐modulatory 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 randomised controlled trial (RCT) using systemic medication in children. Patients/Methods: Multi‐centre, parallel group, assessor‐blind, pragmatic RCT of 36 week duration with a 24 week follow‐up period. 102 children aged 2‐16 years with moderate to severe atopic eczema, unresponsive to topical treatment will be randomised (1:1) to receive methotrexate (MTX; 0.4mg/kg per week) or ciclosporin (CyA; 4mg/kg/day). The trial has co‐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. Analysis plan: The main aims of the trial are to assess whether there is a difference in the speed of onset, effectiveness, side‐effect profile and reduction in flares post‐treatment between CyA and MTX, and, also the cost‐effectiveness of the drugs. Treatment impact on quality of life will also be examined as well as whether FLG genotype influences treatment response. In addition, the trial studies the immune‐metabolic effects of CyA and MTX. Conclusions: The TREAT 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.