Ixekizumab (IXE) is a high affinity monoclonal antibody that selectively targets interleukin-17A. In the SPIRIT-P2 study, IXE every 4 (Q4W) or 2 (Q2W) weeks was superior to placebo (PBO) in improving the signs and symptoms of psoriatic arthritis (PsA) at week 24 in patients with prior inadequate response or intolerance to one or two tumor necrosis factor inhibitors (TNFi). The objective of this study was to determine efficacy and safety of IXE treatment up to 3 years in patients with PsA.
In SPIRIT-P2 (NCT02349295), 310 patients entered the extension period where patients maintained their original ixekizumab dose, and placebo patients received IXEQ4W or IXEQ2W (1:1). Patients failing to demonstrate ≥20% improvement in both tender and swollen joint counts at week 32, or any subsequent visit, were discontinued (mandatory discontinuation criteria). Efficacy outcomes were ACR20/50/70 response, Psoriasis Area and Severity Index (PASI) 75/90/100 response, Leeds Enthesitis Index (LEI), Leeds Dactylitis Index-Basic (LDI-B), minimal disease activity (MDA), and Disease Activity in Psoriatic Arthritis (DAPSA). Ad-hoc efficacy data are presented for intent-to-treat (ITT) patients initially randomized to IXE at week 0. Observed and modified non-responder imputation (missing data treated as non-response for discontinued patients due to lack of efficacy or adverse events [AEs]) was applied to categorical measures. Observed and modified baseline observation carried forward was applied to continuous efficacy measures. Safety was analysed in pts exposed to at least one dose of IXE.
Of the 245 patients initially randomized to IXE at week 0 (ITT), 64 (26.1%) patients discontinued due to lack of efficacy and 22 (9.0%) patients due to mandatory discontinuation criteria. Patients in SPIRIT-P2 who received IXEQ4W and IXEQ2W for 156 weeks reported sustained improvement in ACR responses and manifestations of PsA, including enthesitis, dactylitis, and skin outcomes. Treat-to-target measures such as MDA and DAPSA (low disease activity or remission) were achieved by 30.8% and 47.7% of patients, respectively on IXEQ4W, and by 29.2% and 40.7% of patients, respectively on IXEQ2W. Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity, and 38 out of 337 (5.9%) patients (safety population) discontinued due to AEs. The most common TEAEs were infections (IR=33.1) and injection site reactions (IR=5.4). Three deaths were reported in the study.
In patients treated with IXE who had prior inadequate response or intolerance to one or two TNFi, improvements in the signs and symptoms of PsA persisted up to 3 years. No unexpected safety signals were observed, and the safety profile was consistent with previous studies of IXE.