Functional stabilization with ataluren in ambulatory children with nonsense mutation Duchenne muscular dystrophy: a real-world ambispective cohort study

Absztrakt

Introduction Duchenne muscular dystrophy (DMD) is an X-linked progressive neuromuscular disorder caused by mutations in the DMD gene. Real-world long-term data on ataluren in nonsense mutation DMD (nmDMD) remain limited. Methods This ambispective single-center cohort study included ambulatory patients with genetically confirmed nmDMD and baseline 6-min walk test (6MWT) distance ≥300 m. Patients receiving ataluren plus glucocorticoids were compared with a glucocorticoid-monotherapy group. Outcomes included patient-level change from baseline (COB; last available minus first assessment) in 6MWT and North Star Ambulatory Assessment (NSAA), responder status, loss of ambulation, an exploratory composite functional index, and cardiac and respiratory measures. Results Eighteen patients were included (9 per group). The ataluren-plus-glucocorticoid group showed no significant decline in 6MWT (−10.7 ± 71.7 m; p = 0.676), whereas the monotherapy group declined significantly (−81.7 ± 40.0 m; p = 0.004). The between-group difference favored combination therapy ( p = 0.034), but was attenuated after adjustment for follow-up duration ( p = 0.251). NSAA change was not significantly different between groups ( p = 0.091). The 6MWT responder rate favored combination therapy (66.7% vs. 11.1%; p = 0.050), and the exploratory composite index was higher (+0.50 vs. −0.43; p = 0.013); these secondary findings were exploratory. Loss of ambulation occurred in 55.6% of both groups. No significant between-group differences were observed in cardiac or respiratory outcomes. Discussion/Conclusion In this small ambispective cohort, ataluren plus glucocorticoids was associated with a smaller unadjusted decline in 6MWT distance than glucocorticoid monotherapy. This difference was attenuated after accounting for unequal follow-up duration. No statistically significant between-group difference was observed in NSAA change, and loss of ambulation occurred in the same proportion of patients in both groups. These exploratory findings require confirmation in larger prospective studies.