Dados do Trabalho

Título

LONG TERM FOLLOW-UP OF BRAZILIAN DMD BOYS WITH NONSENSE MUTATIONS INCLUDED IN ATALUREN RANDOMIZED CLINICAL TRIALS.

Introdução

Duchenne Muscular Dystrophy is a genetic X-linked muscular disease. Ataluren has been developed to overcome the genetic defect caused by non-sense mutation. Two of the phase 3 randomized clinical studies have included Brazilian boys. Here we present their follow-up, two years after the end of the studies

Objetivo

To describe the longer-term follow-up of boys included in two Brazilian centers (UFRJ and UFMG), on the randomized clinical trials PTC124-GD-020-DMD (020; NCT1826487) and PTC124-GD-041-DMD (041; NCT03179631).

Método

Cohort follow-up, since inclusion in each study, had an open-label extension, and the sponsor granted all subjects to remain on the medication after the end of the studies. The main endpoints are the ratio of ambulation loss, non-invasive ventilation, cardiomyopathy manifestations, and death. For an exploratory analysis, DMD boys with nonsense-mutation ( nmDMD )from the database of both institutions were used.

Resultados

Five boys from the UFRJ center and four from the UFMG center were included in the studies. Out of these nine patients, two were excluded from our analysis: one because he lost ambulation before starting Ataluren, and the other due to irregular use of medication. The seven patients included in our analysis are currently between 10 and 19 years old (mean age 13). Six are still ambulatory, with a mean age of 12 (range 10-14 years old), and one lost ambulation at 18 years old. Six do not require non-invasive ventilation at mean age 12 (range 10-14 years old), and one initiated non-invasive ventilation at 17 years old. None patients using atualuren died. Databases from the same centers included 34 patients with a nonsense mutation who did not use Ataluren, 21 from UFRJ and 13 from UFMG. Based on the information on endpoints, 7 patients died (ages 15-21), 12 started non-invasive ventilation, and 27 lost ambulation at mean age of 10 years old.

Conclusão

A slower decline rate has been shown in clinical trials and real-world experience, and our results on the longer follow-up are consistent with those.

Referências

Mercuri E. Osorio AN, Muntoni F et al Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015–2022): 2022 interim analysis. J Neurol. 2023; 270(8): 3896–3913.

Palavras Chave

DMD; ataluren; stop codon mutation