Wurster Claudia Diana, Uzelac Zeljko, Dreyhaupt Jens, Schuster Joachim, Dorst Johannes, Ludolph Albert Christian, Wollinsky Kurt
Department of Neurology, Ulm University, Ulm, Germany.
Institute of Human Genetics, Ulm University Medical Center, Ulm, Germany.
Front Neurol. 2024 Apr 3;15:1372674. doi: 10.3389/fneur.2024.1372674. eCollection 2024.
BACKGROUND/OBJECTIVE: Insufficiency of respiratory muscles is the most important reason for mortality in the natural history of SMA. Thus, improvement or stabilization of respiratory function by disease-modifying therapies (DMT) is a very important issue.
We examined respiratory function using forced vital capacity (FVC) in 42 adult SMA patients (2 SMA type 1, 15 SMA type 2, 24 SMA type 3, 1 SMA type 4, median age 37 years, range 17-61 years) treated with nusinersen for a median of 22.1 months (range 2.1 to 46.7 months). Change in FVC was assessed using mixed effects linear regression models.
Baseline FVC differed significantly between SMA type 1 (4.0, 8.0%), 2 (median 22.0%, IQR 18.0-44.0), 3 (median 81.0%, IQR 67.0-90.8) and, respectively, type 4 (84.0%) patients reflecting the heterogeneity of respiratory impairment based on the SMA type in adulthood ( < 0.0001). FVC remained stable during follow-up (mean -0.047, 95% CI -0.115 to 0.020, = 0.17); however, subgroup analysis showed an increase in FVC of type 2 patients (mean 0.144, 95% CI 0.086 to 0.202, < 0.0001) and a decrease in FVC of type 3/4 patients (-0.142, 95% CI -0.239 to -0.044, = 0.005).
The observed improvement in FVC in patients with SMA type 2 can be seen as a therapeutic response differing from the progressive decline typically seen in the spontaneous course. For SMA type 3/4 patients approaching normal spirometry at baseline, FVC may only be of limited use as an outcome parameter due to ceiling effects.
背景/目的：呼吸肌无力是脊髓性肌萎缩症（SMA）自然病程中导致死亡的最重要原因。因此，通过疾病修饰疗法（DMT）改善或稳定呼吸功能是一个非常重要的问题。
我们使用用力肺活量（FVC）对42例成年SMA患者（2例1型SMA、15例2型SMA、24例3型SMA、1例4型SMA，中位年龄37岁，范围17 - 61岁）进行了呼吸功能检查，这些患者接受诺西那生治疗的中位时间为22.1个月（范围2.1至46.7个月）。使用混合效应线性回归模型评估FVC的变化。
1型SMA患者的基线FVC（4.0，8.0%）、2型（中位值22.0%，四分位间距18.0 - 44.0）、3型（中位值81.0%，四分位间距67.0 - 90.8）和4型（84.0%）患者之间存在显著差异，这反映了成年期基于SMA类型的呼吸功能损害的异质性（<0.0001）。随访期间FVC保持稳定（均值 -0.047，95%置信区间 -0.115至0.020，P = 0.17）；然而，亚组分析显示2型患者的FVC有所增加（均值0.144，95%置信区间0.086至0.202，P < 0.00
01），而3/4型患者的FVC有所下降（-0.142，95%置信区间 -0.239至 -0.044，P = 0.005）。
2型SMA患者中观察到的FVC改善可被视为一种不同于自然病程中通常所见的进行性下降的治疗反应。对于基线肺活量测定接近正常的3/4型SMA患者，由于天花板效应，FVC作为结局参数的用途可能有限。
