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

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.

• Authors: Eugenio Mercuri, Francesco Muntoni, Andrés Nascimento Osorio, Már Tulinius, Filippo Buccella, Lauren P Morgenroth, Heather Gordish-Dressman, Joel Jiang, Panayiota Trifillis, Jin Zhu, Allan Kristensen, Claudio L Santos, Erik K Henricson, Craig M McDonald, Isabelle Desguerre, STRIDE, CINRG Duchenne Natural History Investigators
• Journal: Journal of comparative effectiveness research (J Comp Eff Res) Vol. 9 Issue 5 Pg. 341-360 (04 2020) ISSN: 2042-6313 [Electronic] England
• PMID: 31997646 (Publication Type: Journal Article, 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.)

Chemical References

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

Topics

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