Efficacy and safety of ixekizumab (IXE) compared to ustekinumab (UST) in patients with moderate-to-severe plaque psoriasis: A randomised head-to-head trial

IXE (anti-interleukin-17A monoclonal antibody with a high binding affinity) has demonstrated superiority over placebo and etanercept in moderate-to-severe psoriasis over 12 weeks. The objective was to compare efficacy and safety of IXE vs UST (IL-12/23 inhibitor). This multicenter, controlled, double-blind, parallel-group phase 3b trial randomized patients to IXE 80 mg every 2 weeks (IXEQ2W, N=136) or UST 45 mg/90 mg weight-based dosing (N=166). The primary endpoint was the response difference between patients reaching ≥90% Psoriasis Area and Severity Index improvement (PASI90) at 12 weeks, adjusted for treatment, weight, and geographic region. Using the Bonferroni-Hommel procedure, multiplicity-adjusted key secondary endpoints included the static physician global assessment (sPGA), Dermatology Life Quality Index (DLQI), itch numeric rating scale (Itch NRS), and skin pain visual analogue scale (Skin Pain VAS). Treatment-emergent adverse events (TEAEs) were compared using Fishers exact test. IXEQ2W (n=99, 75.0%) was superior to UST (n=70, 42.4%) for PASI90 (response difference: 32.1%; p<.001), PASI75 (90.9%, 69.1%), PASI100 (37.1%, 14.5%), and sPGA(0,1) 2-point response with baseline sPGA ≥3 (86.2%, 57.6%) (multiplicity-adjusted p<.05). The proportion of IXEQ2W vs UST patients who reached sPGA(0) (43.2%, 18.2%) and DLQI(0,1) (62.9%, 44.8%) was significantly higher, with an unadjusted p<.05. There were no significant differences in Itch 4-point response, Itch NRS, and Skin Pain VAS (p>.05). No deaths were reported. There were no statistically significant differences in overall TEAEs (p=.288). IXEQ2W demonstrated superiority over UST, as measured by PASI90, PASI75, PASI 100, and sPGA(0,1). The safety profile seen here is consistent with those previously reported for both treatments.

Dr. Nicole Burkhardt

Dr. Nicole Burkhardt completed her PhD (in 2009) and her postdoctoral studies at the University of Geneva, Switzerland. She is a Senior Clinical Research Scientist at Eli Lilly Australia Pty Ltd, and she has published more than 5 papers in reputed journals.