A 24‐week multicentre, randomized, open‐label, parallel‐group study comparing the efficacy and safety of ixekizumab vs. fumaric acid esters and methotrexate in patients with moderate‐to‐severe plaque psoriasis naive to systemic treatment. (19th November 2019)

• Record Type: Journal Article
• Authors: Reich, K.; Augustin, M.; Thaçi, D.; Pinter, A.; Leutz, A.; Henneges, C.; Schneider, E.; Schacht, A.; Dossenbach, M.; Mrowietz, U.
• Is Part Of: British journal of dermatology. Volume 182:Number 4(2020)
• Page Start: 869
• Page End: 879
• Publication Date: 2019-11-19
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.18384
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Interleukin‐17 antagonists have received a first‐line label for moderate‐to‐severe plaque psoriasis. Objectives: We conducted the first head‐to‐head trial between the two most commonly used first‐line therapies in Germany, fumaric acid esters (FAEs) and methotrexate, and the interleukin‐17A antagonist, ixekizumab. Methods: Systemic‐naive patients were randomized in this parallel‐group, active‐comparator, open‐label, rater‐blinded trial (each group n = 54). The primary outcome was the proportion of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at 24 weeks. Key secondary outcomes included 24‐week PASI 90 and 100, static Physician's Global Assessment (sPGA) score of 0 or 1, and Dermatology Life Quality Index (DLQI) score of 0 or 1. Safety events at week 24 were analysed using Fisher's exact test. Missing data were imputed using nonresponder imputation. The trial was registered at ClinicalTrials.gov (NCT02634801) and EudraCT (2015‐002649‐69). Results: At week 24, more ixekizumab‐treated patients achieved PASI 75 [91% vs. 22% FAEs ( P < 0·001) and 70% methotrexate ( P = 0·014)], PASI 90 [80% vs. 9% FAEs ( P < 0·001) and 39% methotrexate ( P < 0·001)] and PASI 100 [41% vs. 4% FAEs ( P < 0·001) and 13% methotrexate ( P = 0·0041)], as well as sPGA (0, 1) and DLQI (0, 1). Conclusions: Ixekizumab was superior in inducing PASI 75/90/100, sPGA (0, 1) and DLQI (0, 1) responses at week 24 compared with methotrexate and FAEs. Safety profiles for all treatments were consistent with prior studies. Abstract : What's already known about this topic? Fumaric acid esters (FAEs) and methotrexate are two frequently used conventional systemic therapies for chronic plaque psoriasis. A recent meta‐analysis of methotrexate showed a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) rate of 45·2% from primary end points at either 12 or 16 weeks. Until recently, FAEs were licensed for psoriasis only in Germany, but were used in many other European countries as off‐label treatment of psoriasis. In 2017, the European Medicines Agency approved dimethyl fumarate, presumed to be the main active ingredient of FAEs, for the treatment of adult patients with moderate‐to‐severe chronic plaque psoriasis. What does this study add? This study is the first randomized, head‐to‐head trial comparing a biologic treatment with these therapies in a systemic‐treatment‐naive patient population. This study shows the low tolerability of FAEs leading to a significant discontinuation rate, the better tolerability and moderate efficacy of methotrexate, and the good tolerability, fast onset of action and high efficacy of ixekizumab in an unbiased comparison. Our findings reinforce the favourable risk–benefit profile of ixekizumab shown previously and provide further evidence of its efficacy at 24 weeks. Plain language summary available online