Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial

Peter Nash, Bruce Kirkham, Masato Okada, Proton Rahman, Benard Combe, Gerd Ruediger Burmester, David H. Adams, Lisa Kerr, Chin Lee, Catherine L. Shuler, Mark Genovese, Khalid Ahmed, Jeffrey Alper, Nichol Barkham, Ralph E. Bennett, Francisco Javier Blanco García, Ricardo Blanco Alonso, Howard B. Blumstein, Michael S. Brooks, Gerd Rüdiger BurmesterPatricia Cagnoli, Paul H. Caldron, Alain Cantagrel, Der Yuan Chen, Melvin A. Churchill, Christine E. Codding, Benard Combe, Peter M.G. Deane, Jose Del Giudice, Atul A. Deodhar, Rajat K. Dhar, Eva Dokoupilova, Rita M. Egan, Andrea Everding, Eva Galíndez, Mark Genovese, David H. Goddard, Alice Gottlieb, Philippe Goupille, Robert M. Griffin, Ramesh C. Gupta, Stephen Hall, Kalpita Hatti, Mary P. Howell, Yu Huei Huang, Ramina Jajoo, Namieta M. Janssen, Uta Kiltz, Alan J. Kivitz, Steven J. Klein, Mariusz P. Korkosz, Roshan Kotha, Joel M. Kremer, Cummins Lue, José Luis Marenco de la Fuente, Helena Marzo-Ortega, Jordi Gratacós Masmitja, Philip J. Mease, Pier Luigi Meroni, Eric C. Mueller, Anupama C. Nandagudi, Peter Nash, Antonio Fernández-Nebro, Clark M. Neuwelt, Ana Maria Orbai, Meera R. Oza, Deborah L. Parks, Debendra Pattanaik, Maria E. Rell-Bakalarska, David Rosmarin, Euthalia Roussou, Anna I. Rychlewska-Hanczewksa, David H. Sikes, Michael T. Stack, Prashanth Sunkureddi, Hasan Tahir, Diamant Thaçi, Tsen Fang Tsai, Anthony M. Turkiewicz, Leonore Unger, Raúl Veiga Cabello, Ulf Wagner, Cheng Chung Wei, Alvin F. Wells, Peter Youssef, Agnieszka Zielinska

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Abstract

Background Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors. Methods In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295. Findings Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53%] patients; effect size vs placebo 33·8% [95% CI 22·4–45·2]; p<0·0001) and ixekizumab every 2 weeks (59 [48%] patients; 28.5% [17·1–39.8]; p<0·0001) than did patients with placebo (23 [20%] patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported. Interpretation Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab. Funding Eli Lilly and Company.

Original languageEnglish (US)
Pages (from-to)2317-2327
Number of pages11
JournalThe Lancet
Volume389
Issue number10086
DOIs
StatePublished - Jun 10 2017

ASJC Scopus subject areas

  • Medicine(all)

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    Nash, P., Kirkham, B., Okada, M., Rahman, P., Combe, B., Burmester, G. R., Adams, D. H., Kerr, L., Lee, C., Shuler, C. L., Genovese, M., Ahmed, K., Alper, J., Barkham, N., Bennett, R. E., García, F. J. B., Alonso, R. B., Blumstein, H. B., Brooks, M. S., ... Zielinska, A. (2017). Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. The Lancet, 389(10086), 2317-2327. https://doi.org/10.1016/S0140-6736(17)31429-0