@article{01199381bc604e61856e63905c6b12b0,
title = "A Combined Prospective and Retrospective Comparison of Long-Term Functional Outcomes Suggests Delayed Loss of Ambulation and Pulmonary Decline with Long-Term Eteplirsen Treatment",
abstract = "Background: Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care. Objective: To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls. Methods: Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures. Results: Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p < 0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: -3.3 vs. -6.0 percentage points annually, p < 0.0001). Conclusions: Study 405 highlights the functional benefits of eteplirsen on ambulatory and pulmonary function outcomes up to 7 years of follow-up in comparison to external controls.",
keywords = "6-minute walk test, Duchenne muscular dystrophy, dystrophin, eteplirsen, forced vital capacity, loss of ambulation",
author = "Olga Mitelman and Abdel-Hamid, {Hoda Z.} and Byrne, {Barry J.} and Connolly, {Anne M.} and Peter Heydemann and Crystal Proud and Shieh, {Perry B.} and Wagner, {Kathryn R.} and Ashish Dugar and Sourav Santra and James Signorovitch and Nathalie Goemans and McDonald, {Craig M.} and Eugenio Mercuri and Mendell, {Jerry R.}",
note = "Funding Information: The Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study was funded by the United States Department of Education/National Institute on Disability and Rehabilitation Research (#H133B031118, #H133B090001); United States Department of Defense (#W81XWH-12-1-0417); National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (#R01AR061875); Parent Project Muscular Dystrophy. Funding Information: The Italian DMD Registry was funded by the Fon-dazione Telethon (GUP 09010 and GUP 07009). Coinvestigators: Pane M, Mazzone ES, Sormani MP, Messina S, D{\textquoteright}Amico A, Vita G, Fanelli L, Berar-dinelli A, Coratti G, Torrente Y, Frosini S, Norcia G, Rolle E, Magri F, Palermo C, Rossi F, Donati MA, Sacchini M, Arnoldi MT, Baranello G, Mongini T, Pini A, Battini R, Pegoraro E, Previtali S, Bruno C, Politano L, Comi GP, Bertini E, Brogna C. Funding Information: The LNMRC Natural History study has been supported by the Klinisch Onderzoeksfonds UZ Leuven and the Fonds voor Spierzieke Kinderen. Coinvestigator: Marleen van den Hauwe (University Hospitals Leuven, Leuven, Belgium). Funding Information: Studies 201/202 were funded by Sarepta Therapeutics, Inc. and registered on ClinicalTrials.gov under identification numbers NCT01396239 and NCT01540409. Study 405 was funded by Sarepta Therapeutics, Inc. The authors thank the patients and their families for their participation in the studies or registries, and to Fondazione Telethon, Leuven NMRC, and CINRG network sites for making the natural history data available for the present study. The authors also thank Katherine Tsai, MPH, PhD for assistance with Study 405 as a former employee of Sarepta Therapeutics, Inc. Funding Information: Jerry R. Mendell has received grants from the Parent Project Muscular Dystrophy and has received personnel fees from Sarepta Therapeutics, Inc. and National Children{\textquoteright}s Hospital. Publisher Copyright: {\textcopyright} 2022 - The authors. Published by IOS Press.",
year = "2022",
doi = "10.3233/JND-210665",
language = "English (US)",
volume = "9",
pages = "39--52",
journal = "Journal of neuromuscular diseases",
issn = "2214-3599",
publisher = "IOS Press",
number = "1",
}