Real-world outcomes of vosoritide in achondroplasia: A systematic review and meta-analysis of multinational clinical evidence.

PURPOSE: Achondroplasia is the most common skeletal dysplasia, caused by gain-of-function variants in FGFR3, resulting in constitutive receptor activation and downstream inhibition of endochondral ossification. In 2021, the first targeted therapy, vosoritide, was approved in some countries after a landmark randomized trial. Although findings are promising, evidence is limited to modest-sized cohorts. To address this, we conducted a systematic review and meta-analysis of available vosoritide data.

METHODS

A systematic search of PubMed, Cochrane, and Embase was conducted. Data were extracted according to Cochrane guidelines. Outcomes consistently reported were synthesized using R (v4.5) to generate forest plots.

RESULTS

Ten studies were analyzed, encompassing 696 pediatric patients. Meta-analysis of single means showed that height z-score variation after 12 months of treatment was 0.32 (95% CI 0.25-0.40), annualized growth rate was 1.82 cm/year higher after treatment (95% CI 1.46-2.18), and the ratio between sitting height and height showed -0.0089 decrease (95% CI -0.0157 to -0.0020). Studies reported uniform profiles of adverse events, mostly limited to mild injection-site related issues and no serious complications.

CONCLUSION

This meta-analysis shows that real-world observational data on vosoritide in children with achondroplasia replicate clinical trial findings, with greater gains in linear growth and a similarly favorable safety profile.