Background Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease associated with psoriasis, peripheral arthritis, enthesitis, dactylitis, and spondylitis. PsA can be progressive and destructive, resulting in physical deformities, impaired function, decreased quality of life, and increased mortality. Ixekizumab (IXE) is an IgG4 monoclonal antibody that binds with high affinity and specificity to the proinflammatory cytokine IL-17A. Results are presented from a phase 3 trial (SPIRIT-P1; NCT01695239) with IXE in patients with active PsA.
Objectives To explore the impact of IXE, as assessed by disease activity composite measures, up to 52 weeks (wks).
Methods A total of 417 bDMARD-naive adult patients with active PSA, were randomly assigned 1:1:1:1 to subcutaneous administration of either 80-mg IXE every 4 wks (Q4W) or every 2 wks (Q2W), each with a 160-mg starting dose at Wk 0; adalimumab (ADA) 40 mg Q2W (active comparator); or placebo (PBO) in the Double-Blind Treatment Period (DBTP; Wks 0 through 24). Of these patients, 381 continued into the Extension Period (EP; Wks 24 through 52). PBO- and ADA-treated patients were randomly re-assigned (1:1) to 80 mg IXEQ4W or IXEQ2W at Wk 16 (inadequate responders) or Wk 24; ADA-treated patients started IXE, after an 8-wk wash-out period, at Wk 24 (inadequate responders) or Wk 32. Investigators were blinded as to the criteria for inadequate response. Disease activity was measured at Wks 24 and 52 by composite measures including the following: minimum disease activity (MDA) as measured with the Psoriasis Area and Severity Index (MDAPASI) and with the static Physician Global Assessment of psoriasis (MDAsPGA), and modified Composite Psoriatic Disease Activity Indices (CPDAI-12 and CPDAI-14 [see Table 1 footnote]). Analyses for the DBTP were conducted on the Intent-to-Treat Population, defined as all randomly assigned patients; analyses for the EP were conducted on the EP Population, defined as all patients who received at least 1 dose of study drug during the EP. In the DBTP, treatment comparisons were made by a logistic regression model for categorical data with missing values imputed by nonresponder imputation; a mixed model for repeated measures analysis was used for continuous data.
Results At Wk 24, CPDAI-12 and CPDAI-14 total scores (assesses domains of peripheral arthritis, skin disease, enthesitis, dactylitis [and spinal disease for CPDAI-14 only]) for patients receiving IXEQ4W, IXEQ2W, or ADA, were significantly improved compared with results for patients receiving PBO (Table 1). Similarly, at Wk 24, significantly more patients receiving IXEQ4W, IXEQ2W, or ADA achieved MDAsPGA and MDAPASI compared with patients receiving PBO (Table 1), and percentages of patients receiving IXEQ4W or IXEQ2W who achieved MDAsPGA and MDAPASI were sustained through Wk 52 (Table 2). Results for MDAsPGA were similar to results for MDAPASI within each treatment group.
Conclusions IXE provides sustained improvement of disease activity, as measured by various composite measures, for up to 52 wks in bDMARD-naive patients with active PsA.
Disclosure of Interest L. Coates Consultant for: Lilly, M. E. Husni Consultant for: Lilly, Novartis, AbbVie, Celgene, Bristol Myers Squibb, Amgen, Janssen, UCB Pharma, C. Shuler Shareholder of: Lilly, Employee of: Eli Lilly and Company, H. Carlier Shareholder of: Lilly, Employee of: Eli Lilly and Company, C.-Y. Lin Employee of: Eli Lilly and Company, J. Mou Shareholder of: Lilly, Employee of: Eli Lilly and Company, C. Lee Shareholder of: Lilly, Employee of: Eli Lilly and Company, P. Mease Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Consultant for: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Covagen, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Lilly, Pfizer, UCB Pharma