Safety of Risdiplam in Japanese Patients with Spinal Muscular Atrophy: A 12‑Month Interim Analysis of a Postmarketing Surveillance Study.

IF 4.8 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2025-10-01 Epub Date: 2025-08-09 DOI:10.1007/s40120-025-00795-x

Kayoko Saito, Toshio Saito, Reiko Arakawa, Yasuhiro Takeshima, Hisahide Nishio, Yuka Ishikawa, Masahisa Katsuno, Takahiko Tsumuraya, Hiromitsu Kawata, Yuki Miyano, Hirofumi Komaki

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Abstract

Introduction: Risdiplam, an oral splicing modifier for the survival motor neuron-2 gene (SMN2), is approved for treating spinal muscular atrophy (SMA). While its safety and efficacy have been demonstrated in global trials, there are limited real-world data on its safety in Japanese patients with SMA. This all-case postmarketing surveillance (PMS) study aimed to assess the safety and usage patterns of risdiplam in Japan.

Methods: This 12-month interim analysis is part of an ongoing PMS study that includes Japanese patients with SMA who have received risdiplam. The full observation period for this PMS is 24 months from the initiation of risdiplam treatment. Safety data, including adverse drug reactions (ADRs), were collected from case report forms (CRFs) submitted by participating healthcare facilities. ADRs were coded using the MedDRA/J classification.

Results: This study included 538 patients with SMA from 259 institutions in Japan between August 2021 and August 2022. The median age (minimum-maximum) at enrolment was 22.5 (0-83) years, and 51.5% of patients were male. SMA type II (47.2%) and III (27.9%) were the most common phenotypes. The median treatment duration was 366.0 days, and 86.1% of patients continued risdiplam treatment. ADRs were reported in 112 patients (20.8%), while serious ADRs were reported in eight patients (1.5%). The most common ADRs (classified by MedDRA System Organ Class) were gastrointestinal disorders in 86 (16.0%) patients (diarrhoea in 43 [8.0%], faeces soft in 23 [4.3%] and stomatitis in 10 [1.9%] patients). Exploratory analysis suggested that advanced age, comorbidities and concomitant medication use might be associated with an increased incidence of gastrointestinal ADRs.

Conclusions: This 12-month interim analysis of PMS data indicated that risdiplam was well tolerated among Japanese patients with SMA, consistent with previous clinical trial findings. A comprehensive evaluation of the safety and efficacy of risdiplam will be provided in the final 24-month analysis.

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Risdiplam在日本脊髓性肌萎缩症患者中的安全性：一项上市后监测研究的12个月中期分析

Risdiplam是一种口服运动神经元-2存活基因（SMN2）剪接修饰剂，已被批准用于治疗脊髓性肌萎缩症（SMA）。虽然其安全性和有效性已在全球试验中得到证明，但其在日本SMA患者中的安全性的实际数据有限。这项全病例上市后监测（PMS）研究旨在评估瑞斯迪普兰在日本的安全性和使用模式。方法：这项为期12个月的中期分析是一项正在进行的经前综合症研究的一部分，该研究包括接受瑞西泮治疗的日本SMA患者。本次经前综合症的完整观察期为瑞斯地普兰治疗开始后24个月。安全数据，包括药物不良反应（adr），从参与的医疗机构提交的病例报告表（crf）中收集。adr采用MedDRA/J分类进行编码。结果：该研究纳入了2021年8月至2022年8月期间来自日本259家机构的538例SMA患者。入组时中位年龄（最小-最大）为22.5岁（0-83岁），51.5%的患者为男性。SMA II型（47.2%）和III型（27.9%）是最常见的表型。中位治疗持续时间为366.0天，86.1%的患者继续接受利西泮治疗。112例（20.8%）患者报告不良反应，8例（1.5%）患者报告严重不良反应。最常见的不良反应（按MedDRA系统器官分类）为胃肠道疾病86例（16.0%）（腹泻43例（8.0%），大便软质23例（4.3%），口炎10例（1.9%））。探索性分析表明，高龄、合并症和伴随用药可能与胃肠道不良反应发生率增加有关。结论：这项为期12个月的PMS数据中期分析表明，瑞斯地普兰在日本SMA患者中耐受性良好，与之前的临床试验结果一致。在最后的24个月分析中，将对risdiplam的安全性和有效性进行全面评估。

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来源期刊

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. 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