Ixekizumab treatment of biologic-naive patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1)

Objective. The aim was to assess the safety and efficacy of up to 156 weeks of ixekizumab (an IL-17A antagonist) treatment in PsA patients. Methods. In a phase III study, patients naive to biologic treatment were randomized to placebo, adalimumab 40 mg every 2 weeks (ADA; active reference) or ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after an initial dose of 160 mg. At week 24 (week 16 for inadequate responders), ADA (after 8-week washout) and placebo patients were re-randomized to IXEQ2W or IXEQ4W. Outcomes were evaluated using a modified non-responder imputation [linear extrapolation for radiographic progression (modified total Sharp score = 0)] during extended treatment until week 156. Results. Of 417 patients, 381 entered the extension, and 243 of 381 (63.8%) completed the 156-week study. Incidence rates of treatment-emergent and serious adverse events, respectively, were 38.0 and 5.2 with IXEQ2W (n =189) and 38.1 and 8.0 with IXEQ4W (n =197). One death occurred (IXEQ4W). With IXEQ2W and IXEQ4W, respectively, the response rates persisted to week 156 as measured by the ACR response >= 20% (62.5 and 69.8%), >= 50% (56.1 and 51.8%) and >= 70% (43.8 and 33.4%), psoriasis area and severity index (PASI) 75 (69.1 and 63.5%), PASI 90 (64.5 and 51.2%) and PASI 100 (60.5 and 43.6%). Inhibition of radiographic progression also persisted to week 156 in 61% of IXEQ2W and 71% of IXEQ4W patients. Conclusion. In this 156-week study of ixekizumab, the safety profile remained consistent with previous reports, and improvements in signs and symptoms of PsA were observed, including persistent low rates of radiographic progression.