A Combined Prospective and Retrospective Comparison of Long-Term Functional Outcomes Suggests Delayed Loss of Ambulation and Pulmonary Decline with Long-Term Eteplirsen Treatment

Olga Mitelman, Hoda Z. Abdel-Hamid, Barry J. Byrne, Anne M. Connolly, Peter Heydemann, Crystal Proud, Perry B. Shieh, Kathryn R. Wagner, Ashish Dugar, Sourav Santra, James Signorovitch, Nathalie Goemans, Craig M. McDonald, Eugenio Mercuri, Jerry R. Mendell

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)39-52
Number of pages14
JournalJournal of Neuromuscular Diseases
Volume9
Issue number1
DOIs
StatePublished - 2022
Externally publishedYes

Keywords

  • 6-minute walk test
  • Duchenne muscular dystrophy
  • dystrophin
  • eteplirsen
  • forced vital capacity
  • loss of ambulation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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