Efficacy and Safety of Vosoritide for Achondroplasia: A Systematic Review and Dose- Related Meta-Analysis, 2024 Article type: Systematic review and Dose-related Meta-analysis

Abstract

Background Achondroplasia, the most common form of dwarfism, poses significant medical and psychosocial challenges. Vosoritide, a new C-type natriuretic peptide analog, has shown promise in treating achondroplasia by helping bones grow. Therefore, we conducted this study to examine the effect of different vosoritide doses on height from baseline (z-score), annualized growth velocity (AGV), the upper-to-lower body segment ratio (ULBR), and side effects. changes in growth velocity and the frequency of adverse effects. Methods This systematic review and dose-related meta-analyses follow the PRISMA guidelines, which meticulously screen and extract randomized controlled trials (RCTs) from four databases until April 2024 involving 220 patients. We used pairwise meta-analyses and assessed quality using the Cochrane Risk of Bias Tool. Results Higher Vosoritide doses (15 µg/kg or 15–30 µg/kg) showed significantly greater improvements in height z-scores compared to lower doses (2.5 µg/kg or 7.5 µg/kg) or placebo. We observed similar trends for AGV. The 15 µg/kg dose displayed a significantly greater increase compared to both 2.5 µg/kg and 7.5 µg/kg. Interestingly, no significant difference was found between the 15 µg/kg and 30 µg/kg groups, suggesting a possible plateau effect at higher doses. Importantly, both the 15 µg/kg and 15–30 µg/kg groups demonstrated statistically significant improvements in growth velocity compared to placebo. While most comparisons showed no significant changes in ULBR, one study reported a small increase in ULBR with the 15 µg/kg dose compared to the 2.5 µg/kg dose. Adverse effects were mild to moderate across all studies, with no severe effects reported. Conclusion Vosoritide improves achondroplasia growth in a dose-dependent manner. Higher doses (15 µg/kg or 15–30 µg/kg) significantly increased height and growth velocity compared to lower doses or placebo. All adverse effects were mild to moderate. However, the impact on the ULBR and adverse effects require further investigation.