Belančić Andrej, Strbad Tea, Kučan Štiglić Marta, Vitezić Dinko
Department of Clinical Pharmacology, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia.
Department of Basic and Clinical Pharmacology with Toxicology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
J Pers Med. 2024 Feb 24;14(3):244. doi: 10.3390/jpm14030244.
(1) Background: Data on combination or sequential treatment of spinal muscular atrophy (SMA) with disease-modifying drugs (DMDs) are missing and the latter field is poorly understood. The currently available data of patients on risdiplam previously treated with nusinersen are coming from exploratory research mainly focused on safety. Our aim was to investigate the real-world effectiveness (hypothesising non-inferiority) and safety profile of risdiplam in a paediatric-and-adult nusinersen-risdiplam spinal muscular atrophy switch cohort. (2) Methods: A retrospective and anonymous collection of relevant demographic and clinical data for all Croatian SMA patients switched from nusinersen to risdiplam up to September 2023 (reimbursed by Croatian Health Insurance Fund-CHIF) was performed using the CHIF database and associated reimbursement documentation. Patients were included in effectiveness and safety analysis if they met the following inclusion criteria: (i) risdiplam was reimbursed by the CHIF; (ii) the patient received at least six doses of nusinersen before the switch to risdiplam; (iii) there was no relevant pause between the latter disease-modifying drugs; (iv) availability of all prespecified studied data and parameters. (3) Results: In total, 17 patients met the inclusion criteria (58.9% female; median age 12.75 (3.0-44.5) years). In our 'switch' cohort, we demonstrated a non-inferiority of risdiplam to nusinersen in the SMA 1 (+1.0 in CHOP INTEND; = 0.067), SMA 3p (+0.7 in HFMSE; = 0.897), and SMA 3a (+0.8 in RHS; = 0.463) subpopulations, during a one-year follow-up period. There were no reports on respiratory function worsening, feeding worsening, and no lethal events. No new safety concerns were identified, except for the weight gain that arose as a new potential adverse drug reaction 'signal' in two patients. (4) Conclusions: We have reported pivotal real-world findings on switching SMA patients from nusinersen to risdiplam and demonstrated its effectiveness (non-inferiority), safety, and tolerability in a heterogenous paediatric-and-adult 'switch' cohort; this will further increase the quality and standards of care as well as safety of a notable portion of SMA patients, especially for those who demand the switch from nusinersen to other DMDs for clinical or personal reasons.
（1）背景：关于脊髓性肌萎缩症（SMA）使用疾病修饰药物（DMDs）进行联合或序贯治疗的数据缺失，且该领域了解甚少。目前已有的接受过诺西那生治疗后改用利司扑兰的患者数据主要来自探索性研究，重点是安全性。我们的目的是调查利司扑兰在儿科和成人诺西那生-利司扑兰脊髓性肌萎缩症转换队列中的真实世界有效性（假设非劣效性）和安全性。（2）方法：使用克罗地亚健康保险基金（CHIF）数据库及相关报销文件，对截至2023年9月从诺西那生转换为利司扑兰的所有克罗地亚SMA患者的相关人口统计学和临床数据进行回顾性匿名收集。如果患者符合以下纳入标准，则纳入有效性和安全性分析：（i）利司扑兰由CHIF报销；（ii）患者在转换为利司扑兰之前接受了至少六剂诺西那生；（iii）在使用后一种疾病修饰药物之间没有相关停药期；（iv）所有预先指定的研究数据和参数可用。（3）结果：共有17名患者符合纳入标准（女性占58.9%；中位年龄12.75（3.0 - 44.5）岁）。在我们的“转换”队列中，我们证明了在为期一年的随访期内，利司扑兰在SMA 1亚组（CHOP INTEND评分增加1.0；P = 0.067）、SMA 3p亚组（HFMSE评分增加0.7；P = 0.897）和SMA 3a亚组（RHS评分增加0.8；P = 0.463）中不劣于诺西那生。没有关于呼吸功能恶化恶化、喂养恶化的报告，也没有致命事件。除了两名患者出现体重增加这一新的潜在药物不良反应“信号”外，未发现新的安全问题。（4）结论：我们报告了将SMA患者从诺西那生转换为利司扑兰的关键真实世界研究结果，并证明了其在异质性儿科和成人“转换”队列中的有效性（非劣效性）、安全性和耐受性；这将进一步提高相当一部分SMA患者的护理质量和标准以及安全性，特别是对于那些因临床或个人原因要求从诺西那生转换为其他DMDs的患者。
