Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study

J Comp Eff Res. 2020 Apr;9(5):341-360. doi: 10.2217/cer-2019-0171. Epub 2020 Jan 30.

Abstract

Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p ≤ 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.

Keywords: STRIDE Registry; ataluren; dystrophin; effectiveness; nonsense mutation Duchenne muscular dystrophy; safety.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Codon, Nonsense / genetics*
  • Dystrophin / genetics*
  • Humans
  • Muscular Dystrophy, Duchenne / drug therapy*
  • Muscular Dystrophy, Duchenne / genetics
  • Oxadiazoles / adverse effects
  • Oxadiazoles / therapeutic use*
  • Registries
  • Treatment Outcome

Substances

  • Codon, Nonsense
  • DMD protein, human
  • Dystrophin
  • Oxadiazoles
  • ataluren

Associated data

  • ClinicalTrials.gov/NCT02369731