Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1

Abstract

Objective: To assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA).

Methods: Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24.

Results: Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7-66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05).

Conclusions: In biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo.

Trial registration number: NCT01695239; EudraCT2011-002326-49; Results.

Keywords: DMARDs (biologic); Psoriatic Arthritis; Spondyloarthritis; Treatment.

Conflict of interest statement

PJM reports grants and personal fees from Eli Lilly & Company during the conduct of the study. PJM also reports, outside the submitted work, grants, personal fees, and non-financial support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Pfizer and UCB Pharma; grants and personal fees from Merck and Novartis; and non-financial support from Corrona. DvdH reports personal fees from Eli Lilly & Company, during the conduct of the study. DvdH also reports personal fees from AbbVie, Amgen, AstraZeneca, Augurex, Bristol Myers Squibb, Celgene, Centocor, Chugai, Covagen, Daiichi, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma and Vertex, outside the submitted work. DvdH is the director at Imaging Rheumatology BV. CTR reports personal fees from AbbVie, Amgen, Janssen, Novartis, UCB, Boerhinger Ingelheim, as well as grants from Amgen, outside the submitted work. MO reports grants and non-financial support from Eli Lilly & Company, during the conduct of this study. MO also reports non-financial support from Santen Pharmaceutical, Mitsubishi Tanabe Pharma, Pfizer and Abbott Japan, outside the submitted work. RSC and DKB were employees of Eli Lilly & Company, at the time this study was conducted. CLS, C-YL and CHL are employees of Eli Lilly & Company. DDG reports grants and personal fees from AbbVie, Amgen, Celgene, Janssen, Novartis, Pfizer and UCB, and personal fees from Eli Lilly & Company, outside the submitted work.

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Figures

Figure 1

Time course of ACR responses. The percentages of patients achieving ACR20 (A), ACR50 (B) and ACR70 (C) are shown. Patients with inadequate responses to treatment at week 16 or missing data were analysed as non-response up to week 24. aActive reference arm for comparison with placebo. The study was not powered to test equivalence or non-inferiority of ixekizumab versus adalimumab. ACR20/50/70, 20/50/70% American College of Rheumatology response; ADAQ2W, 40 mg adalimumab once every 2 weeks; IXEQ2W, 80 mg ixekizumab once every 2 weeks; IXEQ4W, 80 mg ixekizumab once every 4 weeks; PBO, placebo; Q2W, once every 2 weeks.

Figure 2

Time course of PASI responses. The percentages of patients achieving PASI 75 (A), PASI 90 (B) and PASI 100 (C) are shown. PASI was measured in patients with baseline psoriatic lesion(s) involving ≥3% body surface area. Patients with inadequate responses to treatment at week 16 or missing data were analysed as non-response up to week 24. aActive reference arm for comparison with placebo. The study was not powered to test equivalence or non-inferiority of ixekizumab versus adalimumab. PASI 75/90/100, Psoriasis Area and Severity Index Improvement Response for 75/90/100%; IXEQ2W, 80 mg ixekizumab once every 2 weeks; IXEQ4W, 80 mg ixekizumab once every 4 weeks; Q2W, once every 2 weeks.