Dados do Trabalho

Título

Age at loss of ambulation in patients with DMD from the STRIDE Registry and the CINRG Natural History Study: a matched cohort analysis

Introdução

STRIDE is an ongoing, multicenter, observational registry providing data on ataluren use in nmDMD patients in routine clinical practice

Objetivo

We examined if nonsense mutation Duchenne muscular dystrophy (nmDMD) patients receiving ataluren plus standard of care (SoC) in the Strategic Targeting of Registries and International Database of Excellence (STRIDE) Registry (NCT02369731) experienced a delay in age at loss of ambulation (LOA) versus DMD patients receiving SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (NCT00468832).

Métodos

Data were extracted on January 31, 2021. Propensity score matching identified STRIDE and CINRG patient cohorts (N=241) comparable in established predictors of disease progression: age at first symptoms; age at initiation of corticosteroid use; duration of deflazacort use; and duration of other corticosteroid use. Patients from CINRG who had received investigational drugs for DMD were excluded. Kaplan–Meier analyses were used to estimate age at LOA.

Resultados

The mean (standard deviation) ages at first symptoms in the STRIDE and CINRG cohorts (N=241 per cohort) were 2.7 (1.7) and 2.8 (1.5) years, respectively. Most patients (STRIDE vs CINRG) received corticosteroids for ≥12 months (79.7% per cohort), with a similar proportion receiving deflazacort (43.6% vs 45.2%) or other corticosteroids (41.5% vs 43.2%). In the STRIDE cohort, 24.9% (60/241) of patients lost ambulation compared with 52.7% (127/241) of patients in the CINRG cohort. The median (95% confidence interval) ages at LOA (STRIDE vs CINRG) were 17.9 (14.4, non-estimable) and 12.5 (11.6, 13.5) years, respectively. Kaplan–Meier analyses showed that ataluren plus SoC delayed age at LOA compared with SoC alone (p<0.0001).

Conclusões

These interim registry data show that treatment with ataluren and SoC in routine clinical practice slows disease progression in nmDMD patients.

Palavras Chave

Duchenne Muscular Dystrophy, Loss of Ambulation, Treatment

Declaração de conflito de interesses de TODOS os autores

EM has acted as an advisory board member for AveXis, Biogen, BioMarin, Bristol-Myers Squibb, Ionis Pharmaceuticals, Italfarmaco, Prosensa, PTC Therapeutics, Roche, Santhera Pharmaceuticals, Sarepta Therapeutics and Summit Therapeutics.
FM has received consulting fees from AveXis, Biogen, Dyne Therapeutics, Capricor, Catabasis, Novartis, Pfizer, PTC Therapeutics, Roche, Santhera Pharmaceuticals, Sarepta Therapeutics and Wave Therapeutics, and is supported by the National Institute of Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
FB has received consultancy fees from PTC Therapeutics, Santhera Pharmaceuticals, Sarepta Therapeutics and Pfizer.
ID has received consultancy fees from AveXis, Biogen, BioMarin and PTC Therapeutics.
JK has acted as a consultant for AveXis, Biogen, Ionis Pharmaceuticals, PTC Therapeutics and Roche, and has received research support for taking part in clinical research from Biogen, BioMarin, GlaxoSmithKline, Ionis Pharmaceuticals, Novartis, PTC Therapeutics, Roche, Santhera Pharmaceuticals and Trophos.
ANO has received speaker and consultancy fees from Biogen, PTC Therapeutics and Sarepta Therapeutics, and is an investigator on clinical trials sponsored by Biogen, F. Hoffmann-La Roche, Italfarmaco, Sarepta Therapeutics and TAMDMD.
MT has received lecture fees from Biogen and PTC Therapeutics, and has acted as a consultant on DMD clinical trials for BioMarin, Catabasis Pharmaceuticals, PTC Therapeutics, ReveraGen BioPharma and Sarepta Therapeutics, and as an advisory board member for AveXis, Biogen, Sarepta Therapeutics and PTC Therapeutics.
DM and PT are employees of PTC Therapeutics.
CMM has acted as a consultant on clinical trials of DMD for Astellas, Capricor, Catabasis, Edgewise Therapeutics, Epirium Bio (formerly Cardero Therapeutics), FibroGen, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals and Sarepta Therapeutics. He has received research support for clinical trials from Capricor, Catabasis, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals and Sarepta Therapeutics.
Medical writing and editorial support were funded by PTC Therapeutics Ltd.