EFFICACY AND SAFETY OF IXEKIZUMAB AT WEEK 52 IN BIOLOGIC NAIVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS (SPIRIT-P1)

Abstract

Background: Ixekizumab is a humanised monoclonal antibody, selectively targeting interleukin-17A with high affinity. At 24 weeks, ixekizumab was superior to placebo in achieving American College of Rheumatology (ACR) 20/50/70 response, resolution of enthesitis, dactylitis and inhibiting the progression of structural joint damage in biologic DMARD-naïve patients with active psoriatic arthritis. This analysis investigates the efficacy and safety of ixekizumab after 52 weeks of treatment.

Methods: In a phase III, multicenter, double-blind randomised trial (SPIRIT-P1; NCT01695239), 417 patients were randomised to receive up to 24 weeks of treatment with placebo (N = 106), adalimumab 40mg once every two weeks (Q2W; N = 101), or ixekizumab 80mg every two weeks (Q2W; N = 103) or every four weeks (Q4W; N = 107) following an 160mg initial dose at baseline. Patients who completed the 24 week visit enrolled in the open-label extension period (EP), and received ixekizumab Q4W or Q2W up to one year. Efficacy and safety were analysed using the EP population, i.e. all patients who received at least one dose of study drug. Missing values were imputed by non-response-imputation for categorical variables and modified baseline-observation-carried-forward approach for continuous variables.

Results: A total of 304 patients completed the EP. At week 52 for the Q4W/Q4W and Q2W/Q2W groups, the response rates for ACR 20/50/70 were 69.1/54.6/39.2% and 68.8/53.1/39.6%, respectively. Throughout 52w weeks, minimal changes in mTSS and improvement for enthesitis and dactylitis were observed. The improvement persisted through the EP in the Q4W/Q4W and Q2W/Q2W groups for Psoriasis Area and Severity Index 75/90/100 (78.8/66.7/56.1% and 81.8/78.2/67.3%), the changes from baseline to 52w for percent Body Surface Area involvement of psoriasis were -13.5% and -9.3%, respectively and for Nail Psoriasis Severity Index -16.5 and -21.6, respectively. The number of treatment-emergent adverse events in the EP was comparable to that observed in the first 24-week period; and the majority were mild or moderate in severity, see table for full results.

Conclusion: Over a 52-week period, ixekizumab demonstrated sustained efficacy improving articular signs and symptoms of PsA, as well as plaque-psoriasis and patient reported outcomes with safety comparable to those reported at week 24. This study was sponsored by Eli Lilly and Company.