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.
- DMARDs (biologic)
- Psoriatic Arthritis
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Handling editor Tore K Kvien
Collaborators The authors thank the SPIRIT-P1 study investigators (see online supplementary material for the full investigator list): N Barkham, L Bessette, R Blanco Alonso, EJ Box, M Brooks, R Burgos Vargas, V Chandran, R Dhar, A Fernandez Nebro, R Fleischmann, K Flint, J Forstot, F Galvan Villegas, F Garcia-Fructuoso, O Garmish, M Geneva-Popova, P Geusens, G Gladstein, H Goto, E Griep, R Harrell, A Hou, M Howell, A Kivitz, S Klein, A Kolczewska, M Korkosz, D Lopez Montilla, C Lue, Y Makino, JL Marenco de la Fuente, H Marzo-Ortega, P Mease, T Miyamura, E Mueller, L Myasoutova, F Navarro Sarabia, M Okada, A Ostor, K Papp, L Podrazilova, G Pulka, E-K Raussi, C Ritchlin, J Rosa, E Roussou, A Rychlewska-Hanczewska, K Sada, L Sedova, D Sikes, S Solomon, M Stack, M Stanislavchuk, K Suzuki, H Tahir, J Tälli, A Toncheva, A Turkiewicz, I Valter, S Vladeva, S Wolfe and N Zyablova.
Contributors PJM, CTR, CLS, DKB and DDG were involved in the conception and design of the clinical study; PJM, RSC, CLS and CHL were involved in the acquisition of the data; and all authors were involved in the analysis and interpretation of the data. All authors were involved in the drafting and revising of the manuscript. C-YL was involved in the statistical analysis.
Funding This study was funded and sponsored by Eli Lilly and Company.
Competing interests 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.
Ethics approval The protocol was approved by each site's institutional review board or ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.