芬戈莫德与干扰素β-1a 在儿科多发性硬化症中的对比试验。
Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis.
机构信息
From the Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital, Boston (T.C.); Montreal Neurological Institute, McGill University, and NeuroRx Research - both in Montreal (D.L.A.); Children's Hospital of Philadelphia (B.B.) and the Center for Neuroinflammation and Experimental Neurotherapeutics and the Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania - all in Philadelphia; the Department of Neuropathology (W.B.) and the Department of Pediatrics and Adolescent Medicine, German Center for Multiple Sclerosis in Childhood and Adolescence (J.G.), University Medical Center Göttingen, Göttingen, and the Division of Pediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University, Datteln (K.R.) - all in Germany; Gallarate Hospital, Gallarate, Italy (A.G.); Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London (G.G.); the University of Texas Southwestern Medical Center, Children's Health, Dallas (B.G.), and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.) - both in Texas; Pediatric Multiple Sclerosis Center at NYU Langone, New York (L.K.); Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Paris (M.T.); the Department of Neurology, University of California at San Francisco, San Francisco (E.W.); Novartis Pharmaceuticals, East Hanover, NJ (T.S., Y.C., N.P.); and Novartis Pharma, Basel, Switzerland (M.M.).
出版信息
N Engl J Med. 2018 Sep 13;379(11):1017-1027. doi: 10.1056/NEJMoa1800149.
BACKGROUND
Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.
METHODS
In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 μg per week for up to 2 years. The primary end point was the annualized relapse rate.
RESULTS
Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient).
CONCLUSIONS
Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma; PARADIGMS ClinicalTrials.gov number, NCT01892722 .).
背景
在随机试验中，尚未充分研究年龄小于 18 岁的多发性硬化症患者的治疗方法。我们在此人群中比较了芬戈莫德与干扰素β-1a。
方法
在这项 3 期临床试验中，我们以 1:1 的比例随机分配 10 至 17 岁患有复发性多发性硬化症的患者，每天接受 0.5 毫克的口服芬戈莫德（体重≤40 公斤的患者为 0.25 毫克）或每周接受 30μg 的肌肉内干扰素β-1a，持续 2 年。主要终点是年化复发率。
结果
在总共 215 名患者中，有 107 名被分配接受芬戈莫德治疗，108 名接受干扰素β-1a 治疗。患者的平均年龄为 15.3 岁。在所有患者中，在过去 2 年中平均有 2.4 次复发。调整后的年化复发率为芬戈莫德组 0.12，干扰素β-1a 组 0.67（绝对差异，0.55 次复发；相对差异，82%；P<0.001）。新或新增大 T 加权磁共振成像（MRI）病变的年化发生率是芬戈莫德组的 4.39，干扰素β-1a 组的 9.27（绝对差异，4.88 个病变；相对差异，53%；P<0.001）。接受芬戈莫德治疗的患者中有 88.8%和接受干扰素β-1a 治疗的患者中有 95.3%出现了除多发性硬化症复发以外的不良事件。在芬戈莫德组中，18 名患者（16.8%）出现了严重不良事件，包括癫痫发作（4 例）、感染（4 例）和白细胞减少（2 例）。干扰素β-1a 组中有 7 名患者（6.5%）出现了严重不良事件，包括感染（2 例）和室上性心动过速（1 例）。
结论
在患有复发性多发性硬化症的儿科患者中，与干扰素β-1a 相比，芬戈莫德在 2 年内的复发率较低，MRI 上病变的积累也较少，但严重不良事件的发生率较高。需要更长时间的研究来确定在儿科多发性硬化症中使用芬戈莫德的耐久性和安全性。（由诺华制药公司资助；PARADIGMS 临床试验。gov 编号，NCT01892722）。
Zotero 插件