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.
DEAR EDITOR, Psoriasis is a chronic inflammatory skin disorder, which, in cases of moderate-to-severe disease, requires longterm systemic therapy. 1 For patients with an inadequate response or intolerance to a specific systemic therapy, switching psoriasis treatments is a common practice that may improve outcomes. Switching from conventional to biological therapies is of particular interest, but few head-to-head trials have been performed. 2 The first head-to-head, prospective, randomized trial comparing fumaric acid esters (FAEs) and methotrexate (MTX)two commonly used first-line conventional systemic agentsand an interleukin-17A antagonist, ixekizumab, was published recently. 3 Here we present efficacy and safety results from the extension period of this head-tohead study, in which patients treated with ixekizumab for the first 24 weeks continued with this treatment for up to 60 weeks, and patients treated with FAE or methotrexate up to week 24 were allowed to switch to ixekizumab for a further 36 weeks.This was a phase IIIb, open-label, parallel-group, raterblinded study extension. Patients with moderate-to-severe plaque psoriasis (n = 162) were randomized (1: 1: 1) to FAE, MTX or ixekizumab. 3 Week 24 was reached by 23, 49 and 49 patients on FAE, MTX and ixekizumab, respectively. At week 24, 19 (83%) patients receiving FAE and 31 (63%) patients receiving MTX switched to ixekizumab, while 48 (98%) patients receiving ixekizumab continued treatment. Of these, 18 (95%), 29 (94%) and 45 (94%), respectively, remained in the study to week 60. Missing values were imputed using nonresponder imputation. The efficacy of ixekizumab at week 60 was evaluated for each group as the percentage of patients achieving absolute Psoriasis Area and Severity Index (PASI) 0, ≤ 1, ≤ 2 and ≤ 3. Improvement in quality of life was measured with the Dermatology Life Quality Index (DLQI) (0,1). Safety was assessed throughout the study by the monitoring of adverse events (AEs).Patient baseline demographic and clinical data have been published elsewhere. 3 The most common reason for switching to ixekizumab at week 24 was an inadequate response to FAE
Summary Plaque psoriasis is a skin disease which causes red, scaly patches of skin. It is a chronic disease, which means that it generally persists for a long time. Medications used to treat plaque psoriasis include a drug called methotrexate and, in some European countries, a medicine called fumaric acid esters (FAE). In more recent years, new, powerful drugs called biologics have been used to treat psoriasis. Ixekizumab is one such biologic treatment for moderate‐to‐severe plaque psoriasis. It is an antibody, which means a type of protein that the body's immune system uses to fight off disease. Ixekizumab binds to and neutralises interleukin‐17A, a protein involved in inflammatory responses in the skin that cause psoriasis symptoms. Blocking interleukin‐17A activity in this way is a useful treatment for diseases such as psoriasis. The aim of this study was to compare the efficacy of ixekizumab to methotrexate and FAE in a randomised, controlled trial (RCT) in patients with chronic moderate‐to‐severe plaque psoriasis. A RCT trial means that patients are randomly assigned to a treatment group for one of the drugs being studied, and there is also a control group who do not receive any of the treatments being compared. Efficacy (treatment success) was evaluated using the Psoriasis Area and Severity Index (PASI), a measure of the redness, thickening, scaling, and extent of the psoriatic lesions (affected patches of skin). PASI 75 indicates that a patient experienced at least a 75% improvement in their PASI score since the start of the study. 162 adult patients in Germany were randomly assigned to one of the three treatments. After 24 weeks, 90.7% of patients treated with ixekizumab had achieved PASI 75, compared to 70.4% treated with methotrexate and 22.2% treated with FAE, indicating higher treatment success with ixekizumab. In addition, significantly more patients treated with ixekizumab achieved PASI 90 and PASI 100 (indicating a 90% and 100% improvement in their PASI score, respectively), and had significantly improved Dermatology Life Quality Index (which was measured at multiple time‐points during the trial and measures the patient's quality of life), compared to patients treated with methotrexate or FAE. The percentage of patients who terminated treatment due to adverse health events (unwanted side effects) was lower with ixekizumab compared to FAE (3.7% versus 38.5%), and was similar between ixekizumab and methotrexate (3.7% versus 0.0%). These results confirm the benefit of ixekizumab over methotrexate and FAE as a first‐line treatment for patients with moderate‐to‐severe plaque psoriasis, and may be useful in refining future treatment guidelines. This is a summary of the study: 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
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