Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial

Atul Deodhar, Désirée van der Heijde, Lianne S. Gensler, Tae Hwan Kim, Walter P. Maksymowych, Mikkel Østergaard, Denis Poddubnyy, Helena Marzo-Ortega, Louis Bessette, Tetsuya Tomita, Ann Leung, Maja Hojnik, Gaia Gallo, Xiaoqi Li, David Adams, Hilde Carlier, Joachim Sieper, Frederic Morin, Proton Rahman, Federico ArielAlberto Berman, Judith Carrio, Eleonora Lucero, Jose Maldonado Cocco, Rodolfo Pardo Hidalgo, Jorge Velasco, Diego O. Viola, Johannes Grisar, Heinrich Resch, Clemens Scheinecker, Ana Claudia Melazzi, Luis Roimicher, Antonio Scafuto Scotton, Aaron Alejandro Barrera Rodriguez, Francisco Fidencio Cons Molina, Sergio Duran Barragan, Cassandra M. Skinner, Cesar Francisco Pacheco Tena, Cesar Ricardo Ramos Remus, Juan Cruz Rizo Rodriguez, Seung Jae Hong, Seong Wook Kang, Chang Keun Lee, Eun Bong Lee, Sang Heon Lee, Min Chan Park, Sang Hoon Lee, Eva Dokoupilova, Zdenek Dvorak, Martina Malcova, Karel Pvelka, Kari K. Eklund, Pentti Jarvinen, Anna Karjalainen, Leena Paimela, Yoshinori Taniguchi, Tokutaro Tsuda, Kurisu Tada, Hiroaki Dobashi, Kentaro Inui, Yukitaka Ueki, Yoshifuji Matsumoto, Kazuhiro Hatta, Tatsuya Atsumi, Hitoshi Goto, Shigeru Honjo, Kiyoshi Matsui, Yuya Takakubo, Gunther Neeck, Sylke Wagner, Jürgen Braun, Tomasz Blicharshi, Anna Dudek, Pawel Hrycai, Rafal Plebanski, Janina Drabiszcak-Piatkowska, Jan Brzezicki, Marek Krogulec, Daniela Opris-Belinski, Ana Maria Ramazan, Luminita Tronaru, Marleen G. van de Sande, Galina Matsievskaya, Evgeniya Schmidt, Marina Stanislav, Sergey Yakushin, Olga Ershova, Andrey Rebroy, Melvin A. Churchill, Kathleen P. Flint, Maria Greenwald, Mary P. Howell, Jeffrey L. Kaine, Alan Kivitz, Steven J. Klein, Eric C. Mueller, Eric A. Peters, Roel Querubin, Michael E. Sayers, Craig D. Scoville, Joseph C. Shanahan, Richard Roseff, John E. Hull, Jyothi R. Mallepalli, Mohamed B. Sebai, Steven C. Kimmel, David H. Goddard, Philip J. Mease, Mark D. Harris, Arthur R. Mabaquiao, Roger J. Diegel, Christine Thai, Tania L. Rivera, Amarilis Perez-De Jesus, Oscar Soto-Raices, Ramon Toro-Torres, Carlos Pantojas

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30 Scopus citations

Abstract

Background: Ixekizumab, a high-affinity interleukin-17A (IL-17A) monoclonal antibody, has previously shown efficacy in radiographic axial spondyloarthritis (also known as ankylosing spondylitis). We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, in non-radiographic axial spondyloarthritis. Here, we report the primary results of COAST-X. Methods: COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomly assigned (1:1:1) to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo. Changing background medications or switching to open-label ixekizumab Q2W, or both, was allowed after week 16 at investigator discretion. Primary endpoints were Assessment of SpondyloArthritis international Society-40 (ASAS40) response (defined as an improvement of 40% or more and an absolute improvement from baseline of 2 units or more [range 0–10] in at least three of the four domains [patient global, spinal pain, function, and inflammation] without any worsening in the remaining one domain) at weeks 16 and 52. Patients who switched to open-label ixekizumab were imputed as non-responders in logistic regression analysis. This trial is registered with ClinicalTrials.gov, number NCT02757352. Findings: Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled (105 to placebo, 96 to ixekizumab Q4W, and 102 to ixekizumab Q2W). Both primary endpoints were met: ASAS40 at week 16 (ixekizumab Q4W: 34 [35%] of 96, p=0·0094 vs placebo; ixekizumab Q2W: 41 [40%] of 102, p=0·0016; placebo: 20 [19%] of 105) and ASAS40 at week 52 (ixekizumab Q4W: 29 [30%] of 96, p=0·0045; ixekizumab Q2W: 32 [31%] of 102, p=0·0037; placebo: 14 [13%] of 105). 60 (57%) of 104 patients in the placebo group, 63 (66%) of 96 in the ixekizumab Q4W group, and 79 (77%) of 102 in the ixekizumab Q2W group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events in the ixekizumab groups were nasopharyngitis and injection site reaction. Of the treatment-emergent adverse events of special interest, there was one case of serious infection in the ixekizumab Q4W group. The frequency of serious adverse events was low (four [1%] of 302) and similar across the three groups. There were no malignancies or deaths. No new safety signals were identified. Interpretation: Ixekizumab was superior to placebo for improving signs and symptoms in patients with non-radiographic axial spondyloarthritis at weeks 16 and 52. Reports of adverse events were similar to those of previous ixekizumab studies. Ixekizumab offers a potential therapeutic option for patients with non-radiographic axial spondyloarthritis who had an inadequate response or were intolerant to NSAID therapy. Funding: Eli Lilly and Company.

Original languageEnglish (US)
Pages (from-to)53-64
Number of pages12
JournalThe Lancet
Volume395
Issue number10217
DOIs
StatePublished - Jan 4 2020

ASJC Scopus subject areas

  • Medicine(all)

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