Boyko A N, Boyko O V, Bakhtiyarova K Z, Gusev E I, Dudin V A, Zaslavsky L G, Malkova N A, Parshina Ye V, Poverennova I Ye, Siverceva S A, Totolyan N A, Shchur S G, Fedulov A S, Khabirov F A, Bolsun D D, Zinkina-Orikhan A V, Linkova Yu N, Chernovskaya T V
Pirogov National Medical Research University, Moscow, Russia.
Neuro-Clinic (Yusupov Hospital), Moscow, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2022;122(1):62-71. doi: 10.17116/jnevro202212201162.
To evaluate the efficacy and safety of samPEG-IFN-β1a 180 μg and 240 μg administered once every 2 weeks for the treatment of relapsing remitting multiple sclerosis (RRMS) compared to placebo and low dose interferon beta-1a (LIB) 30 μg administered once weekly. The primary endpoint after 52 weeks of therapy was the time to first relapse, the hypotheses of non-inferiority and superiority to LIB were tested.
This international, multicenter, double blind, comparative, placebo-controlled clinical study enrolled 399 patients with the diagnosis of RRMS, randomized in 4 groups: samPEG-IFN-β1a180 μg (=114), samPEG-IFN-β1a 240 μg (=114), LIB (=114) and placebo (=57). Placebo group patients participated in the study for 20 weeks. After 52 weeks of therapy and 4 weeks of follow-up, LIB group patients completed their participation in the study, patients from PEG-IFN-β1a groups continued to receive therapy until week 100 inclusive. The article presents the results of an analysis conducted after the end of 52 weeks of a double-blind, comparative, randomized, placebo-controlled clinical trial.
Final analysis of the efficacy and safety was performed after 52 weeks of study. Main statistical hypothesis testing proved that both doses of samPEG-IFN-β1a were equally effective when compared to LIB by the primary endpoint - «Time to first relapse». Due to detection of statistically significant differences in the primary endpoint between the study drug and the reference drug, indicating a greater efficacy of the study drug, an additional testing was carried out and the hypothesis of superiority of samPEG-IFN-β1a at a dose of 240 μg over the reference LIB was proved. Evaluation of the dynamics of certain key parameters of magnetic resonance imaging (MRI) of the brain and clinical outcomes demonstrated a positive effect of samPEG-IFN-β1a therapy in the form of decreased activity of the demyelinating process in the brain and reduce the number of relapses. The proportion of patients without new T2 lesions after 52 weeks was 87.6% and 90.4% in 180 μg and 240 μg samPEG-IFN-β1a groups, versus 72.6% in the LIB group (=0.0199 and =0.0033). No progression of multiple sclerosis was shown based on EDSS scale evaluation. During the study, the most common adverse reactions were flu-like symptoms and injection site reactions.
The new drug samPEG-IFN-β1a is an effective and safe agent for relapsing remitting multiple sclerosis treatment, while having an advantage over other low-dose interferons in the form of reduced frequency of intramuscular injections.
评估每2周一次皮下注射180μg和240μg聚乙二醇化干扰素β-1a（samPEG-IFN-β1a）治疗复发缓解型多发性硬化症（RRMS）的有效性和安全性，并与安慰剂及每周一次皮下注射30μg低剂量干扰素β-1a（LIB）进行比较。治疗52周后的主要终点为首次复发时间，检验了非劣效于及优于LIB的假设。
本国际、多中心、双盲、对照、安慰剂对照临床研究纳入399例RRMS患者，随机分为4组：samPEG-IFN-β1a 180μg组（=114例）、samPEG-IFN-β1a 240μg组（=114例）、LIB组（=114例）和安慰剂组（=57例）。安慰剂组患者参与研究20周。治疗52周及随访4周后，LIB组患者完成研究，聚乙二醇化干扰素β-1a组患者继续接受治疗直至第100周。本文呈现了双盲、对照、随机、安慰剂对照临床试验52周结束后的分析结果。
研究52周后进行了有效性和安全性的最终分析。主要统计假设检验证明，与LIB相比，两种剂量的samPEG-IFN-β1a在主要终点“首次复发时间”上同样有效。由于研究药物与对照药物在主要终点上存在统计学显著差异，表明研究药物疗效更佳，因此进行了额外检验，证明240μg剂量的samPEG-IFN-β1a优于对照LIB。对脑部磁共振成像（MRI）某些关键参数动态变化及临床结局的评估表明，samPEG-IFN-β1a治疗具有积极效果，表现为脑部脱髓鞘过程活动减少及复发次数降低。52周后，180μg和240μg samPEG-IFN-β1a组无新T2病灶的患者比例分别为87.6%和90.4%，而LIB组为72.6%（P=0.0199和P=0.0033）。基于扩展残疾状态量表（EDSS）评估未显示多发性硬化进展。研究期间，最常见的不良反应为流感样症状和注射部位反应。
新药samPEG-IFN-β1a是治疗复发缓解型多发性硬化症的有效且安全的药物，与其他低剂量干扰素相比，具有减少肌肉注射频率的优势。
