Günther René, Wurster Claudia Diana, Brakemeier Svenja, Osmanovic Alma, Schreiber-Katz Olivia, Petri Susanne, Uzelac Zeljko, Hiebeler Miriam, Thiele Simone, Walter Maggie C, Weiler Markus, Kessler Tobias, Freigang Maren, Lapp Hanna Sophie, Cordts Isabell, Lingor Paul, Deschauer Marcus, Hahn Andreas, Martakis Kyriakos, Steinbach Robert, Ilse Benjamin, Rödiger Annekathrin, Bellut Julia, Nentwich Julia, Zeller Daniel, Muhandes Mohamad Tareq, Baum Tobias, Christoph Koch Jan, Schrank Bertold, Fischer Sophie, Hermann Andreas, Kamm Christoph, Naegel Steffen, Mensch Alexander, Weber Markus, Neuwirth Christoph, Lehmann Helmar C, Wunderlich Gilbert, Stadler Christian, Tomforde Maike, George Annette, Groß Martin, Pechmann Astrid, Kirschner Janbernd, Türk Matthias, Schimmel Mareike, Bernert Günther, Martin Pascal, Rauscher Christian, Meyer Zu Hörste Gerd, Baum Petra, Löscher Wolfgang, Flotats-Bastardas Marina, Köhler Cornelia, Probst-Schendzielorz Kristina, Goldbach Susanne, Schara-Schmidt Ulrike, Müller-Felber Wolfgang, Lochmüller Hanns, von Velsen Otgonzul, Kleinschnitz Christoph, Ludolph Albert C, Hagenacker Tim
Department of Neurology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dresden, Dresden, Germany.
Lancet Reg Health Eur. 2024 Feb 6;39:100862. doi: 10.1016/j.lanepe.2024.100862. eCollection 2024 Apr.
Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites.
Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded.
Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19-2.25]), 26 months (1.20 [95% CI 0.48-1.91]), and 38 months (1.52 [95% CI 0.74-2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43-1.07]), 26 months (mean difference 0.65 [95% CI 0.27-1.03]), and 38 months (mean difference 0.72 [95% CI 0.25-1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34-43.38]), 26 months (mean difference 29.26 m [95% CI 14.87-43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32-54.09]). No new safety signals were identified.
Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA.
Financial support for the registry from Biogen, Novartis and Roche.
在相对较大的队列中，已证明诺西那生钠在患有5q相关脊髓性肌萎缩症（SMA）的成人中的疗效证据长达16个月，但患者是否会随着时间推移达到平台期仍有待证实。我们在超过38个月的时间里研究了诺西那生钠在成人SMA患者中的疗效和安全性，这是迄今为止来自多个临床地点的一大群患者中的最长时间段。
我们的前瞻性观察性研究纳入了来自德国、瑞士和奥地利的成年SMA患者（2017年7月至2022年5月）。所有参与者均经基因确诊为5q相关SMA，并根据标签接受诺西那生钠治疗。在基线以及治疗开始后14、26和38个月记录总哈默史密斯功能运动量表扩展版（HFMSE）和修订上肢模块（RULM）评分，以及6分钟步行试验（6MWT；米），并比较前后值。还记录了不良事件。
总体而言，389名患者接受了资格筛查，237名患者被纳入。与基线相比，所有结局指标均有显著增加，包括14个月时的平均HFMSE评分（平均差异1.72 [95%CI 1.19 - 2.25]）、26个月时（1.20 [95%CI 0.48 - 1.91]）和38个月时（1.52 [95%CI 0.74 - 2.30]）；14个月时的平均RULM评分（平均差异0.75 [95%CI 0.43 - 1.07]）、26个月时（平均差异0.65 [95%CI 0.27 - 1.03]）和38个月时（平均差异0.72 [95%CI 0.25 - 1.18]），以及14个月时的6MWT（平均差异30.86米[95%CI 18.34 - 43.38]）、26个月时（平均差异29.26米[95%CI 14.87 - 43.65]）和38个月时（平均差异32.20米[95%CI 10.32 - 54.09]）。未发现新的安全信号。
我们的前瞻性、观察性长期（38个月）数据为诺西那生钠在很大一部分成年SMA患者中的持续疗效和安全性提供了进一步的真实世界证据。
该注册研究由百健、诺华和罗氏提供资金支持。
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