Background: Survival among patients with Duchenne muscular dystrophy (DMD) receiving casimersen and golodirsen has not been investigated.
Objective: This study assessed the treatment effect of eteplirsen, casimersen, and golodirsen (phosphorodiamidate morpholino oligomers [PMOs]) on all-cause mortality in patients with DMD using real-world data.
Methods: Objectives were to describe the unadjusted time to death, assess the impact of PMO treatment on survival, and describe frequency of comorbidities prior to death. Sequential target trial emulation (TTE) with inverse probability of treatment and censoring weighting was used to causally compare survival between patients who received glucocorticosteroids (GCs) and eteplirsen, casimersen, or golodirsen (PMO+GCs) or GCs alone (GCs-only). Inovalon closed claims data (January 2016–September 2024) were tokenized and linked with Datavant mortality data.
Results: Twelve of 372 (3%) patients died after treatment initiation for PMO+GCs vs 114/2656 (4%) for GCs-only. In the PMO+GCs group, 208/372 (56%) received eteplirsen, 123/372 (33%) casimersen, and 41/372 (11%) golodirsen. In the TTE analysis, 112 patients initiated PMOs and 2916 initiated GCs-only treatment in the first trial; their median follow-up time was 4.6 and 4.8 years, respectively. In sequential trials, 260 of the patients originally in the GCs-only group initiated treatment with PMOs. Data from 48 sequentially emulated trials estimated that PMO+GCs reduced mortality risk by 69.7% vs GCs-only (hazard ratio: 0.303; 95% CI, 0.119–0.769; P=0.012). In patients from either group with claims in the 3 months before death (n=84), >75% had circulatory/respiratory claims. Median time to death from Kaplan-Meier analysis could not be calculated due to an insufficient number of events.
Conclusions: This study suggests a significantly lower risk of mortality during the observation period in patients with DMD treated with eteplirsen, casimersen, or golodirsen +GCs vs GCs-only, consistent with prior findings for eteplirsen.