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

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.

A phase 4, randomized, head‐to‐head trial comparing the efficacy of subcutaneous injections of brodalumab to oral administrations of fumaric acid esters in adults with moderate‐to‐severe plaque psoriasis (CHANGE)

“…The trials all had similar designs (randomised, open‐label, assessor‐blinded, 24‐week H2H trials), populations (systemic‐naïve, moderate‐to‐severe disease) and outcomes (all confirmed superiority of a first‐line biological treatment over FAE). In all trials, withdrawal rates in the FAE group were high, ranging from 22% to 55.7% 5–8 ; withdrawal rate in CHANGE was 44.8%. However, there was a difference across these trials in how FAE was titrated.…”

“…Four recently published trials also reported H2H comparisons of FAE to a biologic for the treatment of moderate‐to‐severe psoriasis. These were secukinumab, 5 ixekizumab, 6 guselkumab 7 and risankizumab 8 . The trials all had similar designs (randomised, open‐label, assessor‐blinded, 24‐week H2H trials), populations (systemic‐naïve, moderate‐to‐severe disease) and outcomes (all confirmed superiority of a first‐line biological treatment over FAE).…”

“…In Europe, Skilarence® (Almirall, Spain), a product containing only DMF, is approved for treatment of moderate‐to‐severe plaque‐type psoriasis. Therefore, it was relevant to compare FAE and brodalumab, as has also been done for other biologic treatments in plaque psoriasis 5–8 . FAE was recommended as an appropriate comparator by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G‐BA) in Germany for targeted therapies with first‐line label, such as brodalumab, 9 and the present trial was designed in accordance with advice from its health technology assessment committee.…”

Among the brightest antipsoriatic stars

“…However, there are some caveats when interpreting the data. While biologics act very fast, treatment with FAE or DMF shows significant clinical effects beginning at week 12 at the earliest . Full‐dose guselkumab is given from week 0, while FAE are typically uptitrated over a period of 9 weeks (maximum dosage six tablets per day).…”

A subset analysis of efficacy and safety outcomes from phase 3 clinical studies of ixekizumab for the treatment of patients with severe plaque psoriasis

“…In clinical studies, ixekizumab has been shown to be effective in patients with moderate-to-severe chronic plaque psoriasis, demonstrating rapid clinical improvements and a favorable safety profile when compared with placebo [2][3][4][5], and in headto-head studies versus etanercept [2], methotrexate, fumaric acid esters [6], the IL-12/23 inhibitor ustekinumab [7], or the IL-23 inhibitor guselkumab [8]. In phase 3 randomized studies, ixekizumab has been shown to be effective through 60 [9], 108 [10], 156 [11], and 204 [12] weeks of treatment.…”