Treatment with either ixekizumab (IXE) 80 mg every 4 weeks (IXEQ4W) or IXE 80 mg every 2 weeks (IXEQ2W) in patients with psoriatic arthritis (PsA) who had experienced a prior inadequate response or intolerance to tumor necrosis factor inhibitors (TNFis) has shown to be efficacious for up to 52 weeks in key clinical domains, according to the results of the extension phase of the SPIRIT-P2 study (ClinicalTrials.gov identifier: NCT02349295).
At the inception of the extension period (weeks 24-156), any patients being treated with placebo in the double-blind treatment period (weeks 0-24) were rerandomized in a 1:1 ratio to IXEQ2W or IXEQ4W after a 180-mg starting dose. Those study participants receiving IXE in the initial 24-week study maintained their original IXE dose. Results of this extension phase of the SPIRIT-P2 study were published in Rheumatology (Oxford).
The investigators sought to explore the long-term safety and efficacy of the interleukin (IL)-17A antagonist IXE in individuals with active PsA. A total of 310 patients were enrolled in the extension period of the study.
Exposure-adjusted incidence rates (IRs) per 100 patient-years were reported, along with American College of Rheumatology (ACR) responses on an intent-to-treat basis with the use of nonresponder imputation up to week 52.
Between weeks 24 and 156 (228 patient-years of IXE exposure), 140 (IR, 61.3) and 15 (IR, 6.6) patients, respectively, reported infections and serious adverse events (SAEs).
The SAEs included 1 death and 4 serious infections. Among all patients who originally received IXEQ4W and IXEQ2W at week 0 (ie, the nonresponder imputation), ACR 20% improvement criteria (ACR20) responses (61% and 51%, respectively), ACR50 responses (42% and 33%, respectively), and ACR70 responses (26% and 18%, respectively) persisted through week 52.
Patients who were originally treated with placebo and were rerandomized to IXE demonstrated efficacy, based on ACR responses reported at week 52.
The investigators concluded that during the extension phase of the SPIRIT-P2 study, the overall safety profile of IXE in patients with PsA remained consistent with that reported in the 24-week, double-blind period, with clinical improvements in the signs and symptoms of disease continuing for up to 1 year.
The study findings thus support IL-17A antagonism with IXE therapy in those with active PsA who are prior inadequate responders to TNFis.
Genovese MC, Combe B, Kremer JM, et al. Safety and efficacy of ixekizumab in patients with PsA and previous inadequate response to TNF inhibitors: week 52 results from SPIRIT-P2 [published online July 24, 2018]. Rheumatology (Oxford). doi: 10.1093/rheumatology/key182