Background/Purpose: Ixekizumab (IXE) is a high affinity monoclonal antibody that selectively targets IL-17A. In the SPIRIT-P1 phase 3 study (NCT01695239), IXE was superior to placebo (PBO) in achieving ACR20 response at Week 24 in biologic DMARD (bDMARD)-naïve patients with active psoriatic arthritis (PsA). Here, the efficacy and safety of IXE over 2 years in SPIRIT-P1 is evaluated.

Methods: During the SPIRIT-P1 double-blind treatment period (DBTP; Weeks 0-24), 417 bDMARD-naïve patients with active PsA were randomized 1:1:1:1 to 80 mg subcutaneous IXE (160 mg starting dose at Week 0) every 4 weeks (Q4W), every 2 weeks (Q2W), 40 mg adalimumab every 2 weeks (ADA, active reference arm), or PBO. Of these, 381 patients entered the extension period (Weeks 24-52), followed by the long-term extension period (Weeks 52-156). Data presented here are for the combined extension periods (CEP; Weeks 24-108) in patients who completed the initial 24 weeks of treatment and received ≥1 dose of study drug during the CEP (CEP population). IXE-randomized patients continued on IXE throughout the CEP. PBO and ADA patients were re-randomized (1:1) to IXE Q4W or Q2W at Week 16 (inadequate responders) or Week 24; ADA patients had an 8-week washout period before receiving IXE. Patients failing to demonstrate ≥20% improvement in both tender joint count and swollen joint count at Week 32, or any subsequent visit, were discontinued from the study. Efficacy measures included ACR20/50/70 responses, HAQ-Disability Index (DI) Score, DAS 28 based on C-reactive protein (DAS 28-CRP), 75%, 90%, and 100% improvement in the Psoriasis Area and Severity Index (PASI 75/90/100), Leeds Enthesitis Index (LEI), and Leeds Dactylitis Index-Basic (LDI-B). Missing values were imputed by nonresponder imputation for categorical data and modified baseline observation carried forward for continuous data.

Results: Efficacy and safety results for the CEP population are summarized in Table 1. Improvements in ACR and PASI responses, resolution in enthesitis and dactylitis, and improvements from baseline in HAQ-DI, DAS 28-CRP, enthesitis, and dactylitis were observed at Week 108. Frequency of treatment-emergent adverse events (AEs) were similar across treatment arms and the majority were mild or moderate in severity; serious AEs occurred in 46 patients. One death occurred in the CEP population: an ADA/IXE Q4W patient with a history of dyslipidemia, diabetes mellitus, hypertension, and a previous transient ischemic attack, suffered a cerebrovascular accident at Week 108.

Conclusion: For patients naïve to biologic treatment, IXE demonstrated clinically significant improvement in the signs and symptoms of PsA across treatment groups up to 2 years of treatment. The safety profile of IXE observed during the CEP was similar to that observed in the DBTP of SPIRIT-P1 and SPIRIT-P2, as well as other phase 3 studies of IXE in patients with plaque psoriasis.