Efficacy of ixekizumab in patients with psoriatic arthritis: Results of a phase 3 randomized, double-blind, active-and placebo-controlled study

Background/purpose: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease which includes manifestations of peripheral arthritis, enthesitis, dactylitis, and spondylitis, and dermatologic skin and nail changes. Ixekizumab (IXE) is an IgG4 monoclonal antibody that binds with high affinity and specificity to the proinflammatory cytokine IL-17A. Methods: In a phase 3 trial, 417 biologic disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA were randomized to up to 24 weeks of placebo (PBO; n = 106); adalimumab (ADA) 40 mg (n = 101) once every 2 weeks (Q2W; active control); or IXE 80 mg Q2W (n=103) orQ4W (n=107) following 160 mg initial dose atWeek 0. Endpoints assessed at 12 and 24 weeks included response rates for: the American College of Rheumatology (ACR) 20 (primary endpoint), ACR50, ACR70, Psoriasis Area and Severity Index (PASI)75, PASI90, PASI100, and static Physician Global Assessment of psoriasis (sPGA) (0,1 = cleared and/or mild) and sPGA (0 = cleared); and change from baseline in Van der Heijde modified Total Sharp Score (mTSS; assessed at 16 and 24 weeks); and percent change from baseline in body surface area (BSA) psoriasis and Nail Psoriasis Severity Index (NAPSI) scores. Continuous and categorical endpoints were analyzed using the mixed-effect model for repeated measures and logistic regression, respectively. Results: A total of 382 patients completed 24 weeks of the study. Compared to PBO, at 12 and 24 weeks, a significantly greater percentage of patients treated with IXE, both doses, achieved significantly greater responses on the ACR20 (57-62% IXE versus 30% PBO), ACR50, ACR70, PASI75, PASI90, PASI100, and sPGA (0), sPGA (0,1) (all P <.01), and greater improvement of radiographic progression of joint structural damage (P <.025). Both IXE groups had significantly higher percent improvement on BSA and NAPSI (P<.01) versus PBO. Efficacy results with ADA versus PBO were significant on most measures. Incidence rates of adverse events (AE) and serious adverse events were assessed at 24 weeks and were higher for IXE and ADA compared to PBO. Discontinuation due to an AE was similar across all groups. No deaths occurred. Conclusion: In bDMARD-naive patients with active PsA, ixekizumab showed significant clinically meaningful improvements in disease activity, plaque psoriasis and nail clearance, and inhibition of structural progression. Ixekizumab was well tolerated with no unexpected safety findings.