Efficacy of ixekizumab compared to etanercept and placebo in patients with moderate‐to‐severe plaque psoriasis and non‐pustular palmoplantar involvement: results from three phase 3 trials (UNCOVER‐1, UNCOVER‐2 and UNCOVER‐3)

Background Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat. Objective To evaluate the efficacy of ixekizumab in the treatment of patients with moderate‐to‐severe plaque psoriasis and moderate‐to‐severe non‐pustular palmoplantar involvement. Methods In three phase 3, double‐blind, placebo‐controlled trials, patients with moderate‐to‐severe non‐pustular plaque psoriasis [UNCOVER‐1 (N = 1296), UNCOVER‐2 (N = 1224), UNCOVER‐3 (N = 1346)] were randomized to subcutaneous 80 mg ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160‐mg starting dose, or placebo through week 12. Additional UNCOVER‐2 and UNCOVER‐3 cohorts were randomized to 50 mg etanercept biweekly. Patients entering the open‐label long‐term extension (UNCOVER‐3) received ixekizumab Q4W weeks 12–60. Moderate‐to‐severe palmoplantar involvement was defined as Palmoplantar Psoriasis Area and Severity Index (PPASI) ≥8. Results Twenty‐eight percent of UNCOVER‐1, UNCOVER‐2 and UNCOVER‐3 patients had baseline palmoplantar involvement (PPASI ≥0, n = 1092) and 9.1% (n = 350) had moderate‐to‐severe involvement, with mean baseline PPASI ~20, PASI ~24, and most (>60%) had static Physician's Global Assessment ≥4. Higher percentages of patients treated with ixekizumab vs. placebo or etanercept achieved PPASI 50 (approximately 80% vs. 32.9%, 67.8%; ixekizumab, placebo, etanercept, respectively) and PPASI 75 (approximately 70% vs. 18.8%, 44.1%; ixekizumab, placebo, etanercept, respectively) at week 12 (all P < 0.05). PPASI 100 was achieved by higher percentages of ixekizumab‐treated patients vs. placebo (approximately 50% vs. 8.2%, P < 0.001) and ixekizumab Q2W‐treated patients vs. etanercept (51.8% vs. 32.2%, P < 0.05). Outcomes were maintained or improved in patients continuing on ixekizumab Q4W through week 60. Differences between ixekizumab and placebo or etanercept were statistically significant as early as week 1. Conclusion In a subpopulation analysis of patients from phase 3 trials with moderate‐to‐severe non‐pustular palmoplantar involvement and moderate‐to‐severe plaque psoriasis, ixekizumab treatment resulted in greater and more rapid improvements than placebo and etanercept at week 12; improvements were sustained with continued treatment.