Methotrexate shows superiority over ciclosporin for severe paediatric eczema in Trinity trial

A collaboration between researchers at Trinity College Dublin and King’s College London has compared the safety and efficacy of ciclosporin and methotrexate – the first-line drug treatments for atopic dermatitis in children and young people – and found methotrexate to be superior overall.

Reliable data examining the commonly prescribed immune-modulatory drugs has been deficient to date and the study is the largest randomised control trial to reach conclusions regarding a gold standard approach. The findings were published in the British Journal of Dermatology and are anticipated to influence future recommendations and practice.

Prof Carsten Flohr, Chair in Dermatology and Population Health Sciences at King’s College London, and Consultant Dermatologist at St John’s Institute of Dermatology at Guy’s and St Thomas’ NHS Foundation Trust, said the trial “is likely to change our treatment paradigm around this condition, not just for patients in the UK, but also internationally”.

The TREAT (TREatment of severe Atopic Eczema) trial assessed 103 children with severe atopic dermatitis across 13 centres in the UK and Ireland. Participants were aged between two-to-16, unresponsive to topical therapy, and randomised to receive either oral ciclosporin or methotrexate for 36 weeks.

Primary outcomes were any change from baseline to 12 weeks and time to first significant relapse after treatment cessation. Secondary outcomes included changes in quality-of-life from baseline to 60 weeks; number of exacerbations post treatment; and number of patients achieving improvement in Eczema Area and Severity Index, among others.

Results showed that those treated with ciclosporin had a greater improvement between baseline and 12 weeks than those in the methotrexate group, however, there was no notable difference between the two groups at 36 weeks and the Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) of participants in the methotrexate group was significantly lower at 60 weeks.

There was no difference in the number of participants needing to recommence systemic therapy or returning to baseline following treatment cessation in either group, but there was a higher number of reported exacerbations in the cyclosporin group. Methotrexate was also found to be more cost-effective and no concerning safety issues were identified in either group.

Overall, researchers concluded that “participants who received ciclosporin showed a more rapid response to treatment, while methotrexate induced more sustained disease control after discontinuation”. They did, however, note that ciclosporin “may be a better choice where rapid disease control would benefit the participant”.

Prof Alan Irvine, Professor of Dermatology at the School of Medicine and our Lady’s Children’s Hospital, Dublin, said: “Atopic dermatitis is a common condition, affecting more than one-in-five Irish children. When severe it has an enormous impact on the quality-of-life of children and their families. At this stage treatment with creams is no longer effective.

“While innovative new therapies are now available, many European countries, including Ireland, require children to try unlicenced therapies first before they will pay for more advanced treatments. This is the first randomised trial to compare two of these commonly used therapies, methotrexate and ciclosporin, to assess safety and efficacy. We showed both treatments work well and are generally well-tolerated, but methotrexate has more sustained benefit after discontinuing treatment.”