Marzo-Ortega Helena, Sieper Joachim, Kivitz Alan J, Blanco Ricardo, Cohen Martin, Pavelka Karel, Delicha Eumorphia M, Stefanska Anna, Richards Hanno B, Rohrer Susanne
National Institute for Health Research Leeds Biomedical Research Centre, Leeds Teaching Hospitals National Health Service Trust, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
University Clinic Benjamin Franklin, Berlin, Germany.
Lancet Rheumatol. 2020 Jun;2(6):e339-e346. doi: 10.1016/S2665-9913(20)30066-7.
Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin 17A, has shown significant and sustained improvement in the signs and symptoms of ankylosing spondylitis over 3 years in the MEASURE 2 study. We report the 5-year (end-of-study) results of subcutaneous secukinumab 150 mg in the MEASURE 2 study.
MEASURE 2 was a phase 3, double-blind, randomised, placebo-controlled, study done in 13 countries and 53 centres. Patients with ankylosing spondylitis who were 18 years of age or older and fulfilled the modified New York criteria were randomly assigned to receive secukinumab (150 mg or 75 mg) or placebo subcutaneously at baseline and weeks 1, 2, and 3, and then every 4 weeks from week 4. At week 16, patients initially given placebo were randomly assigned again (placebo switchers) to receive secukinumab 150 mg or 75 mg. Efficacy results are reported for patients initially randomised to secukinumab 150 mg and those who switched from placebo to secukinumab 150 mg at week 16. An optional dose escalation from secukinumab 75 mg to 150 mg was initiated beginning week 140. We assessed efficacy endpoints at week 260 (5 years), including Assessment of Spondyloarthritis International Society (ASAS) 20 and ASAS 40, inactive disease according to ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, Short Form-36 Physical Component Summary, and ASAS partial remission. Analyses were stratified by anti-tumour necrosis factor (TNF) status (anti-TNF-naive and anti-TNF inadequate response). The safety analysis included all patients who received one dose or more of secukinumab. We report data as observed without accounting for missing data. The MEASURE 2 study was registered with ClinicalTrials.gov, NCT01649375.
219 patients were randomly assigned during the trial and 150 (68%) completed 5 years of treatment, including 82 (77%) of 106 patients in the secukinumab 150 mg group and 68 (65%) of 105 in the secukinumab 75 mg group. Efficacy analysis in the secukinumab 150 mg group included 53 patients who completed the study and one additional patient who was assessed in the treatment period weeks 212-260, but did not complete the study. 134 (61%) of 219 patients were anti-TNF-naive and 85 (39%) were anti-TNF inadequate responders. ASAS responses at 5 years with secukinumab 150 mg were 36 (67%) of 54 patients (ASA20) and 27 (50%) patients (ASAS40). Sustained improvement was observed across other efficacy endpoints with secukinumab 150 mg at 5 years. At 5 years, the proportion of patients achieving efficacy endpoints of BASDAI 50 response was 53% (44/83); ASAS 5/6 response was 51% (42/83); ASDAS-CRP inactive disease was 21% (17/81); and ASAS partial remission was 25% (21/83). Exposure-adjusted incidence rates with any secukinumab dose for selected adverse events were 1·0 per 100 patient-years (95% CI 0·4-1·9) for Candida infections, 0·5 (0·1-1·2) for Crohn's disease, 0·4 (0·1-1·1) for ulcerative colitis, 0·6 (0·2-1·4) for major adverse cardiovascular events, 0·5 (0·1-1·2) for uveitis, and 0·6 (0·2-1·4) for malignant or unspecified tumours.
Secukinumab 150 mg provided sustained improvement in the signs, symptoms, and physical function in patients with ankylosing spondylitis after 5 years of treatment. The safety profile of secukinumab remained consistent with previous reports.
Novartis Pharma.
司库奇尤单抗是一种直接抑制白细胞介素17A的全人源单克隆抗体，在MEASURE 2研究中，其在3年时间里显著且持续改善了强直性脊柱炎的体征和症状。我们报告了MEASURE 2研究中皮下注射150 mg司库奇尤单抗的5年（研究结束时）结果。
MEASURE 2是一项3期、双盲、随机、安慰剂对照研究，在13个国家的53个中心开展。年龄在18岁及以上且符合改良纽约标准的强直性脊柱炎患者被随机分配，在基线、第1、2和3周皮下注射司库奇尤单抗（150 mg或75 mg）或安慰剂，然后从第4周开始每4周注射一次。在第16周时，最初接受安慰剂治疗的患者再次被随机分配（安慰剂转换者）接受150 mg或75 mg司库奇尤单抗治疗。报告了最初随机分配至150 mg司库奇尤单抗组以及在第16周从安慰剂转换至150 mg司库奇尤单抗组患者的疗效结果。从第140周开始启动了从75 mg司库奇尤单抗至150 mg的可选剂量递增。我们在第260周（5年）评估了疗效终点，包括国际脊柱关节炎协会（ASAS）20和ASAS 40、根据强直性脊柱炎疾病活动评分结合C反应蛋白（ASDAS-CRP）评估的非活动疾病、巴斯强直性脊柱炎疾病活动指数（BASDAI）、BASDAI50、巴斯强直性脊柱炎测量指数、巴斯强直性脊柱炎功能指数、简明健康调查问卷躯体健康评分以及ASAS部分缓解。分析按抗肿瘤坏死因子（TNF）状态（未使用过TNF抑制剂和使用TNF抑制剂疗效不佳）进行分层。安全性分析纳入了所有接受过一剂或更多剂司库奇尤单抗治疗的患者。我们按观察到的数据报告，未对缺失数据进行处理。MEASURE 2研究已在ClinicalTrials.gov注册，注册号为NCT01649375。
在试验期间，219例患者被随机分配，150例（68%）完成了5年治疗，其中司库奇尤单抗150 mg组106例患者中有82例（77%），司库奇尤单抗75 mg组105例患者中有68例（65%）。司库奇尤单抗150 mg组的疗效分析纳入了53例完成研究的患者以及1例在治疗期第212 - 260周接受评估但未完成研究的患者。219例患者中，134例（61%）未使用过TNF抑制剂，85例（39%）使用TNF抑制剂疗效不佳。使用司库奇尤单抗150 mg治疗5年时，54例患者中有36例（67%）达到ASAS20反应，27例（50%）患者达到ASAS40反应。在5年时，使用司库奇尤单抗150 mg在其他疗效终点均观察到持续改善。在5年时，达到BASDAI 50反应疗效终点的患者比例为53%（44/83）；ASAS 5/6反应为51%（42/83）；ASDAS-CRP非活动疾病为21%（17/81）；ASAS部分缓解为25%（21/83）。选定不良事件的任何司库奇尤单抗剂量的暴露调整发病率分别为：念珠菌感染每100患者年1.0例（95%CI 0.4 - 1.9），克罗恩病0.5例（0.1 - 1.2），溃疡性结肠炎0.4例（0.1 - 1.1），主要不良心血管事件0.6例（0.2 - 1.4），葡萄膜炎0.5例（0.1 - 1.2），恶性或未明确肿瘤0.6例（0.2 - 1.4）。
治疗5年后，司库奇尤单抗150 mg使强直性脊柱炎患者的体征、症状和身体功能得到持续改善。司库奇尤单抗的安全性概况与既往报告一致。
诺华制药。
