Real-world growth outcomes and safety of vosoritide in children with achondroplasia: a Brazilian single center 24 monhts experience.

Abstract

Introduction: To evaluate the longitudinal effects of vosoritide on growth, body proportionality, and safety in children with achondroplasia in a real-world clinical setting, and to identify early predictors of treatment response.

Methods: We conducted a hybrid retrospective-prospective observational study in children with achondroplasia treated with vosoritide at a single tertiary center. Pre-treatment clinical and anthropometric data were collected retrospectively and prospectively. Prospectively patients were evaluated at baseline and after 12 and 24 months on treatment. Growth was assessed using height SDS, based on both WHO and achondroplasia-specific reference charts, as well as annualized height velocity Z-scores (HV SDS). Body proportionality was evaluated using the height/(height - sitting height) ratio. Longitudinal changes were analyzed using linear mixed-effects models, and potential predictors of response were explored using correlation and regression analyses.

Results: Thirty-five children (mean age 5.92 ± 3.56 years) were included. Height velocity increased significantly at both 12 months (+1.50 SDS) and 24 months (+1.91 SDS) compared with baseline (p < 0.001). Using achondroplasia-specific references, height SDS increased over time, with a trend toward increment at 12 months (+0.17 SDS, p = 0.060) and a significant increase at 24 months (+0.50 SDS, p < 0.001). Similarly, WHO-based height SDS showed no significant change at 12 months and a significant increment at 24 months (+0.30 SDS, p = 0.005), suggesting a more gradual shift toward WHO standards. Body proportionality remained unchanged (p = 0.134). Height velocity increment during the first 12 months did not significantly predict height SDS gain at 24 months, highlighting inter-individual variability in treatment response. A significant age-by-time interaction was observed (p = 0.006), suggesting a differential longitudinal response according to age at treatment initiation. Hypertrichosis occurred in 66% of patients, but no severe adverse events were reported.

Conclusion: Vosoritide increased linear growth in this real-world cohort, with heterogeneous response patterns over time. Height velocity increment during the first 12 months did not predict longer-term outcomes, and body proportionality remained unchanged over 24 months. Treatment was well tolerated, supporting its use in clinical practice.