Continuing versus withdrawing ixekizumab treatment in patients with axial spondyloarthritis who achieved remission: efficacy and safety results from a placebo-controlled, randomised withdrawal study (COAST-Y)
Robert Landewé, Lianne S. Gensler, Denis Poddubnyy, Proton Rahman, Maja Hojnik, Xiaoqi Li, Soyi Liu Leage, David H. Adams, Hilde Carlier, Filip Van den Bosch, Federico Javier Ariel, Alberto Berman, Judith Carrio, Eleonora Del Valle Lucero, Jose Maldonado Cocco, Benito Jorge Velasco, Heinrich Resch, Johannes Grisar, Valderilio Azevedo, Mauro Keiserman, Flora Marcolino, Ricardo Xavier, Antonio Ximenes, Ana Melazzi, Antonio Scotton, Louis Bessette, Walter Maksymowych, Frederic Morin, Eva Dokoupilova, Zdenek Dvorak, Vlastimil Racek, Radka Moravcova, Martina Malcova, Karel Pavelka, Kari K. Eklund, Pentti Jarvinen, Leena Paimela, Philippe Goupille, Eric Lespessailles, Bernard Combe, Gunther Neeck, Jürgen Braun, Andrea Everding, Regina Cseuz, Edit Drescher, Yolanda Braun Moscovici, Ori Elkayam, Yair Molad, Tatiana Reitblat, Carlo Salvarani, Tetsuya Tomita, Yoshinori Taniguchi, Hiromichi Tamaki, Tokutaro Tsuda, Kurisu Tada, Hiroaki Dobashi, Tadashi Okano, Kentaro Inui, Yukitaka Ueki, Yoshifuji Matsumoto, Yoshinobu Koyama, Tatsuya Atsumi, Hitoshi Goto, Yuya Takakubo, Yeon-Ah Lee, Ji Hyeon Ju, Seong Wook Kang, Tae-Hwan Kim, Chang Keun Lee, Eun Bong Lee, Sang Heon Lee, Min-Chan Park, Kichul Shin, Sang-Hoon Lee, Aaron Alejandro Barrera Rodriguez, Fidencio Cons-Molina, Sergio Duran Barragan, Cassandra Michelle Skinner, Cesar Francisco Pacheco Tena, Cesar Ricardo Ramos Remus, Juan Cruz Rizo Rodriguez, Marleen G. van de Sande, Eduard Griep, Malgorzata Szymanska, Tomasz Blicharski, Jan Brzezicki, Anna Dudek, Pawel Hrycaj, Rafal Plebanski, Artur Racewicz, Rafal Wojciechowski, Marek Krogulec, Daniela Opris-Belinski, Ana Maria Ramazan, Galina Matsievskaya, Evgeniya Schmidt, Tatiana Dubinina, Marina Stanislav, Sergey Yakushin, Olga Ershova
Abstract
OBJECTIVES: The objective of COAST-Y was to evaluate the effect of continuing versus withdrawing ixekizumab (IXE) in patients with axial spondyloarthritis (axSpA) who had achieved remission. METHODS: COAST-Y is an ongoing, phase III, long-term extension study that included a double-blind, placebo (PBO)-controlled, randomised withdrawal-retreatment period (RWRP). Patients who completed the originating 52-week COAST-V, COAST-W or COAST-X studies entered a 24-week lead-in period and continued either 80 mg IXE every 2 (Q2W) or 4 weeks (Q4W). Patients who achieved remission (an Ankylosing Spondylitis Disease Activity Score (ASDAS)<1.3 at least once at week 16 or week 20, and <2.1 at both visits) were randomly assigned equally at week 24 to continue IXE Q4W, IXE Q2W or withdraw to PBO in a blinded fashion. The primary endpoint was the proportion of flare-free patients (flare: ASDAS≥2.1 at two consecutive visits or ASDAS>3.5 at any visit) after the 40-week RWRP, with time-to-flare as a major secondary endpoint. RESULTS: Of 773 enrolled patients, 741 completed the 24-week lead-in period and 155 entered the RWRP. Forty weeks after randomised withdrawal, 83.3% of patients in the combined IXE (85/102, p<0.001), IXE Q4W (40/48, p=0.003) and IXE Q2W (45/54, p=0.001) groups remained flare-free versus 54.7% in the PBO group (29/53). Continuing IXE significantly delayed time-to-flare versus PBO, with most patients remaining flare-free for up to 20 weeks after IXE withdrawal. CONCLUSIONS: Patients with axSpA who continued treatment with IXE were significantly less likely to flare and had significantly delayed time-to-flare compared with patients who withdrew to PBO.