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

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).

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).

Método

STRIDE is an ongoing, multicenter, observational registry providing data on ataluren use in nmDMD patients in routine clinical practice. Data were extracted on January 31, 2022. Propensity score matching identified STRIDE and CINRG patient cohorts (N=260) 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 e Conclusões

The mean (standard deviation) ages at first symptoms in the STRIDE and CINRG cohorts (N=260 per cohort) were 2.8 (1.7) and 2.8 (1.5) years, respectively. Most patients (STRIDE vs CINRG) received corticosteroids for ≥12 months (85.0% vs 83.8%), with a similar proportion receiving deflazacort (47.7% vs 44.2%) or other corticosteroids (41.9% vs 43.5%). In the STRIDE cohort, 26.5% (69/260) of patients lost ambulation compared with 54.6% (142/260) of patients in the CINRG cohort. The median (95% confidence interval) ages at LOA (STRIDE vs CINRG) were 17.9 (14.8, not estimable) and 12.5 (12.0, 13.5) years, respectively. Kaplan–Meier analyses showed that ataluren plus SoC delayed age at LOA compared with SoC alone (p<0.0001). These Kaplan–Meier analyses showed that in routine clinical practice ataluren plus SoC delayed age at LOA by 5.4 years compared with SoC alone in patients with nmDMD.

Palavras Chave

Duchenne muscular dystrophy. Nonsense mutation. Ambulation.

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.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.
APC, DSM and AF are employees of PTC Therapeutics.