Efficacy and safety of fumaric acid esters in young patients aged 10-17 years with moderate-to-severe plaque psoriasis: a randomized, double-blinded, placebo-controlled trial

Background Apart from biologics, no systemic drugs are approved in Europe for children with moderate-to-severe psoriasis. Retrospective observational studies have shown promising results for fumaric acid esters (FAE) in this setting. Objectives To show superiority of FAE over placebo in terms of treatment response after 20 weeks in children and adolescents aged 10-17 years. Methods In a multicentre, randomized, double-blind, placebo-controlled phase IIIb study, patients aged 10-17 years with moderate-to-severe plaque psoriasis requiring systemic therapy were randomized 2 : 1 to receive FAE (n = 91) or placebo (n = 43) over 20 weeks, followed by an open-label FAE treatment phase. The coprimary endpoints were >= 75% improvement in Psoriasis Area and Severity Index (PASI 75) and Physician's Global Assessment (PGA) score of 0 or 1 (clear or almost clear) at week 20. The study was registered with EudraCT number 2012-000035-82. Results At week 20, 55% [95% confidence interval (CI) 0 center dot 44-0 center dot 65] of FAE-treated patients achieved a PASI 75 response vs. 19% (95% CI 0 center dot 08-0 center dot 33) in the placebo group (absolute difference 36%, 95% CI 0 center dot 20-0 center dot 53; P < 0 center dot 001). In total, 42% (95% CI 0 center dot 32-0 center dot 53) in the FAE group vs. 7% (95% CI 0 center dot 01-0 center dot 19) in the placebo group achieved a PGA score of 0 or 1 at week 20 (absolute difference 35%, 95% CI 0 center dot 21-0 center dot 49; P < 0 center dot 001). During the double-blind period, drug-related adverse events occurred more frequently in patients receiving FAE compared with placebo (76% vs. 47%). Gastrointestinal disorders were the most common adverse events. Conclusions FAE administered over a period of 20 weeks demonstrated a better response than placebo; the difference was statistically significant and clinically meaningful. Application up to 40 weeks was generally well tolerated. However, further studies are required.

Automated summary

This study demonstrated that fumaric acid esters (FAE) showed superior treatment response compared to placebo in children and adolescents aged 10-17 with moderate-to-severe psoriasis after 20 weeks, with generally good tolerability. However, further studies are needed to confirm these findings.