192例接受诺西那生治疗的脊髓性肌萎缩症（SMA）成年患者的呼吸功能——一项多中心观察性研究。
Respiratory function in 192 adult patients with spinal muscular atrophy (SMA) treated with nusinersen - a multicenter observational study.
作者信息
Wurster Claudia D, Stolte Benjamin, Kessler Tobias, Freigang Maren, Bjelica Bogdan, Ilse Benjamin, Koch Jan C, Cordts Isabell, Mensch Alexander, Zeller Daniel, Uzelac Zeljko, Sam Georges, Lapp Hanna Sophie, Wohnrade Camilla, Rödiger Annekathrin, Muhandes Mohamad Tareq, Schneider Ilka, Bellut Julia, Nentwich Julia, Dorst Johannes, Schuster Joachim, Schreiber-Katz Olivia, Osmanovic Alma, Totzeck Andreas, Thimm Andreas, Steinbach Robert, Grosskreutz Julian, Kleinschnitz Christoph, Ludolph Albert C, Deschauer Marcus, Kirschner Janbernd, Dreyhaupt Jens, Wollinsky Kurt, Petri Susanne, Weiler Markus, Hagenacker Tim, Günther René
机构信息
Institute of Human Genetics, Ulm University and Ulm University Medical Center, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
Department of Neurology, Ulm University Medical Center, Ulm, Germany.
出版信息
Orphanet J Rare Dis. 2025 Sep 8;20(1):476. doi: 10.1186/s13023-025-04009-3.
BACKGROUND
Natural history data show that respiratory function is impaired in SMA patients. Observational studies have shown stabilization of respiratory function in adult SMA patients treated with nusinersen. However, long-term studies investigating the effect of nusinersen on respiratory function in adult SMA patients are rare.
METHODS
We examined respiratory function using forced vital capacity of predicted normal (FVC%), FVC in liters, capacity per second (FEV1) and peak expiratory flow (PEF) in 192 adult SMA patients treated with nusinersen for a median of 3.2 years (IQR: 2.1–4.0, range: 0.2–5.2). Changes in spirometric parameters were analyzed using individual linear regression models separate in each patient to estimate the slope. Additionally, three multivariable models were performed to assess the effect of age, sex, treatment duration, baseline FVC% and each one of the variables of interest (1) SMA type, (2) ambulation status, (3) spondylodesis on follow-up FVC%. Associations between respiratory parameters and motor function (HFMSE) were investigated via Scatter plots and Spearman’s rank correlation.
RESULTS
Spirometric parameters remained stable during treatment (median annual rate of change of FVC% 0.17% ( = 0.40), FVC in liters -0.002 ( = 0.59), FEV1 -0.014 l ( = 0.06) and PEF 0.025 l/s ( = 0.65)). In all multivariable models, age, sex, treatment duration, SMA type, ambulation status, and spondylodesis showed no significant association with follow-up FVC%. No significant correlations were observed between respiratory and motor function.
CONCLUSION
Respiratory parameters remained stable during treatment with nusinersen in adult SMA patients over several years.
CLINICAL TRIAL NUMBER
Not applicable.
背景
自然史数据显示，脊髓性肌萎缩症（SMA）患者的呼吸功能受损。观察性研究表明，接受诺西那生治疗的成年SMA患者呼吸功能稳定。然而，关于诺西那生对成年SMA患者呼吸功能影响的长期研究很少。
方法
我们使用预计正常用力肺活量（FVC%）、升为单位的FVC、每秒容量（FEV1）和呼气峰值流速（PEF），对192例接受诺西那生治疗的成年SMA患者进行呼吸功能检查，治疗时间中位数为3.2年（四分位间距：2.1 - 4.0，范围：0.2 - 5.2）。使用个体线性回归模型对每位患者分别分析肺量计参数的变化，以估计斜率。此外，还进行了三个多变量模型，以评估年龄、性别、治疗持续时间、基线FVC%以及每个感兴趣的变量（1）SMA类型、（2）行走状态、（3）脊柱融合术对随访FVC%的影响。通过散点图和Spearman等级相关性研究呼吸参数与运动功能（HFMSE）之间的关联。
结果
治疗期间肺量计参数保持稳定（FVC%的年变化中位数为0.17%（= 0.40），升为单位的FVC为 - 0.002（= 0.59），FEV1为 - 0.014升（= 0.06），PEF为0.025升/秒（= 0.65））。在所有多变量模型中，年龄、性别、治疗持续时间、SMA类型、行走状态和脊柱融合术与随访FVC%均无显著关联。呼吸与运动功能之间未观察到显著相关性。
结论
成年SMA患者在接受诺西那生治疗的数年中，呼吸参数保持稳定。
临床试验编号
不适用。
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