Muscle Nerve. 2022 Jun 18. doi: 10.1002/mus.27662. Online ahead of print.
INTRODUCTION/AIMS: Pulmonary decline is an important issue in patients with Duchenne muscular dystrophy (DMD). Eteplirsen is a US-approved treatment for patients with DMD and exon 51 skip-amenable mutations. Previous analyses have shown that eteplirsen is associated with statistically significant attenuation of pulmonary decline. This study evaluates the effect of eteplirsen treatment from newly available data sources on pulmonary function over time in patients with DMD.
METHODS: This study uses a post hoc pooled analysis to compare the percentage of predicted forced vital capacity (FVC%p) and projected time to pulmonary function milestones in patients with DMD and exon 51 skip-amenable mutations receiving eteplirsen (Studies 204 and 301) or standard of care (SoC; Cooperative International Neuromuscular Research Group Duchenne Natural History Study). A mixed model for repeated measures framework was applied to evaluate the impact of eteplirsen.
RESULTS: An average annual rate of FVC%p decline for eteplirsen-treated patients was estimated to be 3.47%, which was a statistically significant attenuation from the 5.95% rate of decline estimated in SoC patients (P = 0.0001). Using linear extrapolations of the model-estimated decline in FVC%p, the attenuation in FVC%p decline for eteplirsen-treated patients corresponded to a delay of 5.72 years in time to needing continuous ventilation, 3.31 years in time to needing nighttime ventilation, and 2.11 years in time to needing a cough assist device compared with SoC patients.
DISCUSSION: The attenuation of FVC%p decline suggests that eteplirsen-treated patients experienced statistically significant and clinically meaningful attenuations in pulmonary decline compared with SoC patients. This article is protected by copyright. All rights reserved.