Efficacy and safety of c-type natriuretic peptide analogues in children with achondroplasia: A systematic review and meta-analysis of randomised clinical trials

Objectives: Achondroplasia is a genetic skeletal disorder characterised by impaired endochondral ossification and disproportionate short stature. C-type natriuretic peptide (CNP) analogues have emerged as targeted therapies to improve growth outcomes; however, comparative evidence across agents remains limited. Material and Methods: A systematic review and meta-analysis of randomised controlled trials (RCTs) was conducted to evaluate the efficacy and safety of CNP-based therapies in children with achondroplasia. The primary outcome was annualised growth velocity (AGV) at 52 weeks. Secondary outcomes included height Z-score, upper-to-lower body segment ratio and safety outcomes. Random-effects models with Hartung–Knapp adjustment were applied, and an exploratory network meta-analysis (NMA) was performed. Results: Four RCTs were included. CNP-based therapies significantly improved AGV compared with placebo (mean difference [MD] = 1.39 cm/year; 95% confidence interval [CI]: 0.89–1.90). Height Z-score also improved (MD = 0.28; 95% CI: 0.24–0.33), while no significant change was observed in body proportionality. There was no significant difference in safety outcomes; however, injection-site reactions were more frequent. NMA showed that both vosoritide and navepegritide were superior to placebo, with no significant difference between agents. Conclusion: CNP-based therapies improve growth outcomes with an acceptable safety profile and should be integrated into multidisciplinary care. Further head-to-head studies are needed.