Saito Kayoko, Saito Toshio, Arakawa Reiko, Takeshima Yasuhiro, Nishio Hisahide, Ishikawa Yuka, Katsuno Masahisa, Tsumuraya Takahiko, Kawata Hiromitsu, Miyano Yuki, Komaki Hirofumi
Institute of Medical Genetics, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku City, Tokyo, 162-8666, Japan.
Division of Child Neurology, Department of Neurology, NHO Osaka Toneyama Medical Center, Osaka, Japan.
Neurol Ther. 2025 Aug 9. doi: 10.1007/s40120-025-00795-x.
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.
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.
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.
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.
利司扑兰是一种用于生存运动神经元2基因（SMN2）的口服剪接修饰剂，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实，但关于其在日本SMA患者中的安全性的真实世界数据有限。这项全病例上市后监测（PMS）研究旨在评估利司扑兰在日本的安全性和使用模式。
这项为期12个月的中期分析是一项正在进行的PMS研究的一部分，该研究纳入了接受利司扑兰治疗的日本SMA患者。该PMS的完整观察期为从利司扑兰治疗开始起24个月。安全性数据，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使用MedDRA/J分类进行编码。
本研究纳入了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。入组时的中位年龄（最小-最大）为22.5（0-83）岁，51.5%的患者为男性。II型（47.2%）和III型（27.9%）SMA是最常见的表型。中位治疗持续时间为366.0天，86.1%的患者继续接受利司扑兰治疗。112例患者（20.8%）报告了ADR，8例患者（1.5%）报告了严重ADR。最常见的ADR（按MedDRA系统器官分类）是86例（16.0%）患者出现胃肠道疾病（43例[8.0%]腹泻，23例[4.3%]大便变软，10例[1.9%]患者出现口腔炎）。探索性分析表明，高龄、合并症和同时使用药物可能与胃肠道ADR的发生率增加有关。
这项对PMS数据的12个月中期分析表明，利司扑兰在日本SMA患者中耐受性良好，这与先前的临床试验结果一致。将在最后的24个月分析中提供对利司扑兰安全性和有效性的全面评估。
