Background Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease associated with psoriasis, peripheral arthritis, enthesitis, dactylitis, and spondylitis. Ixekizumab (IXE) is an IgG4 monoclonal antibody that binds with high affinity and specificity to the proinflammatory cytokine IL-17A. Results are presented for the phase 3 trial (SPIRIT-P1) with IXE treatment of patients with active PsA.
Objectives To evaluate the efficacy and safety of IXE when used alone or in combination with concomitant conventional DMARDs (cDMARDs).
Methods A total of 417 bDMARD-naive adult patients were randomly assigned 1:1:1:1 to subcutaneous administration of 80-mg IXE every 4 wks (Q4W) or every 2 wks (Q2W), each starting with a 160-mg dose at Wk 0; adalimumab (ADA) 40 mg Q2W (active comparator); or placebo (PBO) during the Double-Blind Treatment Period (DBTP; Wks 0 through 24). Of these patients, 267 were receiving a concomitant cDMARD at baseline, 149 were not, and 1 did not receive study drug; patients were stratified by cDMARD use, and were to remain on their cDMARD through the DBTP. At Wk 24, efficacy was evaluated by American College of Rheumatology (ACR) response; and progression of structural damage was assessed by the modified Total Sharp Score (mTSS). Safety assessments included the percentage of patients experiencing treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuations due to adverse events (AEs). Efficacy analyses were conducted on the Intent-to-Treat Population, defined as all randomly assigned patients; safety analyses were conducted on the Safety Population, defined as all randomly assigned patients who received at least 1 dose of study drug. Fisher's test was used for treatment comparisons in ACR and AE data, and an analysis of covariance model was used for mTSS data. Missing values were imputed by nonresponder imputation for ACR data and by linear extrapolation for mTSS data.
Results At Wk 24, compared with patients receiving PBO, significantly more patients receiving IXEQ4W or IXEQ2W (with/without concomitant cDMARD) achieved ACR20/50/70 responses (see Table for ADA results). Patients receiving IXEQ2W (with/without concomitant cDMARD) or IXEQ4W or ADA (with concomitant cDMARD) showed significantly less progression in mTSS from baseline compared with patients receiving PBO (Table). No treatment-by-subgroup effects were observed for ACR20/50/70 or mTSS (Table footnotes). In patients receiving concomitant cDMARDs, significantly more patients receiving IXE or ADA experienced ≥1 TEAE, compared with patients receiving PBO; the percentages of patients with SAEs or discontinuations due to an AE were comparable among treatment groups (Table).
Conclusions IXE demonstrated efficacy in improvement of PsA signs and symptoms and structural inhibition in bDMARD-naive patients with/without concomitant cDMARD use. With concomitant cDMARD use, although significantly more patients receiving IXE or ADA experienced ≥1 TEAE, compared with patients receiving PBO, the frequency of SAEs and discontinuations due to an AE were comparable among all treatment groups.
Disclosure of Interest L. Coates Consultant for: Lilly, A. Gottlieb Grant/research support from: Centocor (Janssen), Amgen, Abbott (Abbvie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, Merck, Xenoport, Dermira, Consultant for: Amgen, Astellas, Akros, Centocor (Janssen), Celgene, Bristol Myers Squibb, Beiersdorf, Abbot Labs (AbbVie), TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor, Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSLK Behring Biotherapies for Life, Glaxo Smith Kline, Xenoport, Catabasis, Meije Seika Pharma, Takeda, Mitsubishi Tanabe Pharma Development America, Genentech, C. Shuler Shareholder of: Lilly, Employee of: Eli Lilly and Company, C.-Y. Lin Employee of: Eli Lilly and Company, S. Samanta Shareholder of: Lilly, Employee of: Eli Lilly and Company, S. Moriarty 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, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Pfizer, UCB Pharma