Real-world growth outcomes and safety of vosoritide in children with achondroplasia: a Brazilian single center 24 monhts experience.
Vosoritide increased height velocity and height SDS in children with achondroplasia over 24 months, but responses varied significantly among individuals.
Where it sits
this study against the rest of the vosoritide corpusSummary and findings
This study evaluated the effects of vosoritide on growth and safety in children with achondroplasia over 24 months. Thirty-five children with a mean age of 5.92 ± 3.56 years were treated and assessed at baseline, 12 months, and 24 months. Significant increases in height velocity and height SDS were observed at 12 and 24 months compared to baseline.
Abstract
<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion(s)</h4>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.
Background
This paper addresses the effects of vosoritide on growth in children with achondroplasia, a condition characterized by disproportionate short stature. Previous studies have indicated potential benefits of vosoritide, but real-world data on its long-term effects and safety in a clinical setting are limited. Understanding the longitudinal impact of this treatment is crucial for clinicians considering its use.
Methods
This was a hybrid retrospective-prospective observational study conducted at a single tertiary center. The study included 35 children with achondroplasia, with pre-treatment data collected retrospectively and follow-up data collected prospectively at baseline, 12 months, and 24 months. Primary outcomes included changes in height SDS and height velocity Z-scores, assessed using linear mixed-effects models.
Results
At 24 months, height velocity increased significantly by +1.91 SDS compared to baseline (p < 0.001). Height SDS increased significantly by +0.50 SDS (p < 0.001) using achondroplasia-specific references, while WHO-based height SDS showed a significant increase of +0.30 SDS at 24 months (p = 0.005). Body proportionality remained unchanged (p = 0.134).
Interpretation
The findings suggest that vosoritide can lead to significant increases in height velocity and height SDS over 24 months in children with achondroplasia. However, the effect sizes, while statistically significant, may not be clinically meaningful for all patients, especially given the variability in individual responses. The study's limitations, including its small sample size and single-center nature, may restrict the applicability of these results to broader populations.
Key findings
- Height velocity increased significantly at 12 months (+1.50 SDS) and 24 months (+1.91 SDS) compared with baseline (p < 0.001).
- Height SDS increased at 24 months (+0.50 SDS, p < 0.001) using achondroplasia-specific references.
- WHO-based height SDS showed a significant increment at 24 months (+0.30 SDS, p = 0.005).
- Body proportionality remained unchanged (p = 0.134).
- Hypertrichosis occurred in 66% of patients, but no severe adverse events were reported.
Limitations
- single-center study
- small sample size n=35
- no long-term follow-up beyond 24 months
- no control group for comparison
- observational design limits causal inferences