Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A Systematic Review.

Background: Vamorolone has recently been approved for the management of Duchenne muscular dystrophy to replace glucocorticosteroids, which theoretically have more side effects. However, its efficacy and safety profile is unclear.

Objective: We aimed to assess the efficacy of vamorolone in Duchenne muscular dystrophy through the 6-minute walk test (6MWT), the North Star Ambulatory Assessment (NSAA), time to stand velocity (TTSTAND), time to run 10 m (TTRW), time to climb four stairs (TTCLIMB) and a safety profile.

Methods: A systematic search was conducted in MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to June 2024 (PROSPERO: CRD42024558413) for studies evaluating the effect or safety profile of vamorolone in a population with Duchenne muscular dystrophy on 6MWT, NSAA and TTSTAND. TTRW, TTCLIMB and a safety profile were included. The risk of bias was assessed using the Cochrane Collaboration's risk of bias tool (RoB2) and the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group from the US National Institutes of Health National Heart, Lung, and Blood Institute, depending on the type of design. Results were expressed as mean differences or proportions with 95% confidence intervals (CIs), depending on the outcome.

Results: Six studies with a total of 145 individuals with Duchenne muscular dystrophy and a baseline age between 4.7 and 5.5 years were included in the systematic review. Overall, the most effective dose was 6 mg/kg/day. At 24 weeks, this dose showed a statistically significant effect compared with the untreated cohorts of 41.60 m (95% CI 14.30, 68.90) on the 6MWT, 3.57 points (95% CI 1.89, 5.25) on the NSAA, 0.06 events/s (95% CI 0.02, 0.10) on the TTSTAND, approximately 0.25 m/s on the TTRW and 0.04 (95% CI -0.00, 0.08) to 0.07 events/s (95% CI 0.03, 0.11) on the TTCLIMB. There was some discrepancy in the statistical significance of some studies, although the direction of the effect was usually similar. In general, the effect was maintained in the extension studies. Adverse events were less frequent than in historical cohorts treated with glucocorticoids. Finally, the risk of bias in the included studies was low.

Conclusions: According to our results, vamorolone offers a statistically and clinically significant benefit in the management of Duchenne muscular dystrophy, with fewer side effects than glucocorticoids. However, the number of studies limits the interpretability and generalisability of these data, requiring more studies with more participants to perform a meta-analysis.