荷兰莱顿大学医学中心Désirée van der Heijde研究组在研究中取得进展，他们发现Ixekizumab可有效治疗非放射学中轴型脊柱关节炎患者。该研究2019年12月5日在线发表在国际一流学术期刊《柳叶刀》上。

Ixekizumab是一种高亲和力的白细胞介素-17A（IL-17A）单抗，可有效治疗强直性脊柱炎。

COAST-X是一项为期52周的随机、双盲、安慰剂对照、平行研究，在欧洲、亚洲、北美和南美15个国家的107个研究点进行。2016年8月2日至2018年1月29日，研究组共招募了303名非放射学中轴型脊柱关节炎成人患者，均对非甾体抗炎药无响应或不耐受。将其按1:1:1随机分组，其中105名皮下注射安慰剂，96名皮下注射Ixekizumab，每4周注射80mg（Q4W），102名注射Ixekizumab，每2周注射80mg（Q2W）。

治疗16周后，Ixekizumab Q4W组的国际脊柱关节炎协会-40（ASAS-40）缓解率为35%，Ixekizumab Q2W组为40%，安慰剂组为19%。治疗52周后，Ixekizumab Q4W组ASAS-40缓解率为30%，Ixekizumab Q2W组为31%，安慰剂组为13%。

安慰剂组有57%的患者发生至少一次因治疗引起的不良事件，Ixekizumab Q4W组为66%，Ixekizumab Q2W组为77%。Ixekizumab组中最常见的突发性不良反应为鼻咽炎和注射部位反应，其中Ixekizumab Q4W组中有1例严重感染。严重不良事件的发生率较低，且三组间相差不大。三组均未发生恶性肿瘤或死亡事件。

总之，Ixekizumab治疗非放射学中轴型脊柱关节炎患者在16周和52周的疗效均优于安慰剂，为非甾体抗炎药无响应或不耐受的患者提供了一种新选择。

附：英文原文

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

Author: Atul Deodhar, Désirée van der Heijde, Lianne S Gensler, Tae-Hwan Kim, Walter P Maksymowych, Mikkel stergaard, 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 Ariel, Alberto 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

Issue&Volume: December 05, 2019

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.

DOI: 10.1016/S0140-6736(19)32971-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32971-X/fulltext