A Head-to-Head Comparison of Ixekizumab and Adalimumab in Biologic-Naive Patients with Active Psoriatic Arthritis: Efficacy and Safety Outcomes from a Randomized, Open-Label, Blinded Assessor Study

Aims: In SPIRIT H2H, ixekizumab (IXE) was superior to adalimumab (ADA) at Week (Wk)24 for simultaneous achievement of ACR50 and PASI100 in patients (pts) with active PsA. We report final Wk52 efficacy and safety, and efficacy in subgroups defined by concomitant MTX use. Methods: Pts with active PsA fulfilling CASPAR criteria, ≥3/66 tender and ≥ 3/68 swollen joints, ≥3% psoriasis BSA involvement, no prior treatment with bDMARDs, and prior inadequate response to ≥1 conventional synthetic DMARD, were randomized 1:1 to open‐label IXE or ADA (baseline BSA≥10%, PASI≥12, and sPGA≥3) through 52wks. Outcomes included the percentage of pts simultaneously achieving ACR50 + PASI100, ACR20/50/70, PASI75/90/100, NAPSI = 0, MDA, VLDA, defined as MDA 7/7, DAPSA LDA, DAPSA remission, LEI = 0, SPARCC Enthesitis Index = 0, LDI‐B = 0, and HAQ‐DI ≥0.35 change from baseline. Nine pts with active PsO and BSA≥3% were assessed as PASI = 0 at baseline, a medical inconsistency that was resolved using medical judgement. These patients were considered PASI100 responders if PASI = 0 and BSA = 0 at post baseline visits. Results: Overall, 87% of IXE (N = 283) and 84% of ADA (N = 283) pts randomized completed Wk52. IXE provided significantly greater response than ADA for simultaneous ACR50 + PASI100 through Wk52. Simultaneous ACR50 + PASI100 response with IXE was numerically greater than ADA, regardless of concomitant MTX use. Treatment by MTX use interaction was significant for ACR20/50/70 at Wk52 (P = 0.019, P = 0.016, P = 0.011, respectively). Treatment‐emergent adverse events (AEs) occurred in 73.9% and 68.6% of pts, serious AEs occurred in 4.2% and 12.4%, and discontinuations due to AEs occurred in 4.2% and 7.4% for IXE and ADA, respectively. Conclusion: IXE provided significantly greater simultaneous joint and skin improvement vs. ADA through Wk52. IXE performed at least as well as ADA across multiple PsA domains including musculoskeletal and skin domains through Wk52. Safety outcomes for IXE and ADA were consistent with their previously established safety profiles.