Kiliç Mehmet Akif, Kürekçi Fulya, Kipoğlu Osman, Coşkun Orhan, Karacebey Burçin Nazlı, Katar Selahattin, Avci Rıdvan, Genç Hülya Maraş, Çakir Erkan, Yildiz Edibe Pembegül
Department of Pediatric Neurology, Faculty of Medicine, İstanbul University, İstanbul, Turkiye.
Department of Pediatric Pulmonology, Faculty of Medicine, İstinye University, İstanbul, Turkiye.
Turk J Med Sci. 2025 Feb 2;55(3):702-709. doi: 10.55730/1300-0144.6018. eCollection 2025.
BACKGROUND/AIM: Available data regarding the effects of nusinersen on respiratory function in the real-world setting are uncertain. We aimed to evaluate the impact of nusinersen on respiratory outcomes over a follow-up period of up to 72 months in patients with symptomatic spinal muscular atrophy type 1 (SMA type 1).
Respiratory status was defined similarly to previous studies: spontaneous breathing, noninvasive ventilatory support for ≤16 h per day, and permanent assisted ventilation. The planned evaluation time was day 180 (after the fourth dose), day 300 (after the fifth dose), and after the last injection for patients who received nusinersen for 2 years or more.
Our cohort consisted of 32 patients. The mean age at treatment initiation was 6.6 months (range: 2.5-16 months). Twenty-eight of 32 patients were eligible for evaluation after the fourth dose. Twenty-three of 28 patients were eligible for assessment after the fifth dose of nusinersen. Eight received nusinersen for 2 years or more (range: 26-72 months). At the last assessment, four patients did not require ventilatory support between the ages of 30 and 81 months. One was successfully weaned from invasive ventilatory support after the tenth dose of nusinersen. The respiratory status of most patients remained stable or worsened following the fourth and fifth doses of nusinersen. There were no significant differences in respiratory status between patients who received nusinersen at 6 months of age or younger and those older than 6 months, after the fourth and fifth doses of nusinersen (p > 0.05).
Improvement in respiratory function in patients treated with nusinersen for 2 years or more is generally not expected in the natural course of the disease. However, in our cohort, patients treated with nusinersen mainly maintained their current respiratory status, and many patients required ventilatory support despite treatment with nusinersen. Therefore, our findings may reflect the limited efficacy of nusinersen in symptomatic patients.
背景/目的：关于在现实环境中，诺西那生对呼吸功能影响的现有数据并不确定。我们旨在评估诺西那生对1型症状性脊髓性肌萎缩症（SMA 1型）患者长达72个月随访期内呼吸结局的影响。
呼吸状态的定义与既往研究类似：自主呼吸、每天无创通气支持≤16小时以及长期辅助通气。计划评估时间为第180天（第四剂后）、第300天（第五剂后），以及接受诺西那生治疗2年或更长时间患者的最后一次注射后。
我们的队列由32名患者组成。开始治疗时的平均年龄为6.6个月（范围：2.5 - 16个月）。32名患者中有28名在第四剂后符合评估条件。28名患者中有23名在第五剂诺西那生后符合评估条件。8名患者接受诺西那生治疗2年或更长时间（范围：26 - 72个月）。在最后一次评估时，4名患者在30至81个月龄之间不需要通气支持。1名患者在第十剂诺西那生后成功脱离有创通气支持。在第四剂和第五剂诺西那生后，大多数患者的呼吸状态保持稳定或恶化。在6个月及以下接受诺西那生治疗的患者与6个月以上患者之间，第四剂和第五剂诺西那生后的呼吸状态无显著差异（p>0.05）。
在疾病的自然病程中，一般不期望接受诺西那生治疗2年或更长时间的患者呼吸功能得到改善。然而，在我们的队列中，接受诺西那生治疗的患者主要维持其当前呼吸状态，并且许多患者尽管接受了诺西那生治疗仍需要通气支持。因此，我们的研究结果可能反映了诺西那生在有症状患者中的疗效有限。
