サイトウ　カヨコ   Saitou Kayoko   齋藤　加代子    所属   医学部 医学科（東京女子医科大学病院）    職種   特任教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA).
掲載誌名	正式名：Journal of neurology 略　 称：J Neurol ISSNコード：14321459/03405354
掲載区分	国外
巻・号・頁	pp.1-16
国際共著	国際共著
著者・共著者	Oskoui Maryam, Day John W, Deconinck Nicolas, Mazzone Elena S, Nascimento Andres, Saito Kayoko, Vuillerot Carole, Baranello Giovanni, Goemans Nathalie, Kirschner Janbernd, Kostera-Pruszczyk Anna, Servais Laurent, Papp Gergely, Gorni Ksenija, Kletzl Heidemarie, Martin Carmen, McIver Tammy, Scalco Renata S, Staunton Hannah, Yeung Wai Yin, Fontoura Paulo, Mercuri Eugenio,
発行年月	2023/02
概要	Risdiplam is an oral, survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and non‑ambulant type 3 SMA. The primary endpoint was met: a significantly greater change from baseline in 32-item Motor Function Measure (MFM32) total score was observed with risdiplam compared with placebo at month 12. After 12 months, all participants received risdiplam while preserving initial treatment blinding. We report 24-month efficacy and safety results in this population. Month 24 exploratory endpoints included change from baseline in MFM32 and safety. MFM‑derived results were compared with an external comparator. At month 24 of risdiplam treatment, 32% of patients demonstrated improvement (a change of ≥ 3) from baseline in MFM32 total score; 58% showed stabilization (a change of ≥ 0). Compared with an external comparator, a treatment difference of 3.12 (95% confidence interval [CI] 1.67-4.57) in favor of risdiplam was observed in MFM-derived scores. Overall, gains in motor function at month 12 were maintained or improved upon at month 24. In patients initially receiving placebo, MFM32 remained stable compared with baseline (0.31 [95% CI - 0.65 to 1.28]) after 12 months of risdiplam; 16% of patients improved their score and 59% exhibited stabilization. The safety profile after 24 months was consistent with that observed after 12 months. Risdiplam over 24 months resulted in further improvement or stabilization in motor function, confirming the benefit of longer-term treatment.
DOI	10.1007/s00415-023-11560-1
PMID	36735057