Supplementary Material for: The CrescNet Registry Achondroplasia Module: Real-World Demographic Data and Clinical Outcomes in Untreated and Vosoritide-Treated Individuals

Introduction: Achondroplasia is a rare skeletal dysplasia characterized by severe disproportionate short stature. Vosoritide is currently the only approved therapy. The CrescNet registry is a network of primary and specialized pediatric tertiary centers that aims to improve early detection of growth disorders in Europe. In 2021, an achondroplasia-specific data collection module was set up within CrescNet to enhance data collection among children with achondroplasia and assess the impact of interventions. Here, we describe the module setup and report preliminary real-world outcomes of vosoritide treatment over 3 years. Methods: The module was established in 10 of 11 countries participating in CrescNet. Achondroplasia-specific data were collected, including developmental milestones, interventions (such as limb-lengthening surgery, treatment with vosoritide and growth hormone), complications, and health-related quality of life, alongside standard anthropometric measurements (eg height, weight, etc). Pseudonymized data were sent to the CrescNet central database, Leipzig University Hospital, Germany, for analysis by age and treatment status. Results: As of May 2025, 486 participants from 32 tertiary centers were enrolled. Data from 73 untreated and 186 vosoritide-treated individuals with genetically documented achondroplasia were analyzed. In vosoritide-treated individuals, mean height standard deviation score, referenced to an untreated European achondroplasia population, significantly increased from baseline at 1, 2, and 3 years after vosoritide initiation (P≤0.0001). Conclusions: The module facilitates the collection of real-world data to improve understanding of the natural history of achondroplasia and outcomes associated with interventions. Growth data from vosoritide-treated individuals were consistent with clinical trial findings and published real-world data. Longer-term follow-up is ongoing.引言：软骨发育不全（Achondroplasia）是一种罕见的骨骼发育异常疾病，以严重的不成比例身材矮小为核心临床特征。目前，沃索肽（Vosoritide）是唯一获批的治疗药物。CrescNet登记系统是由欧洲基层儿科医疗点与专科儿科三级中心组成的网络，旨在提升该地区生长发育障碍的早期筛查效能。2021年，CrescNet内部搭建了针对软骨发育不全的专用数据采集模块，以强化软骨发育不全患儿的数据收集工作，并评估各类临床干预措施的实际效果。本文详述了该模块的搭建流程，并报告了沃索肽治疗3年的初步真实世界研究结果。 研究方法：该模块在参与CrescNet的11个国家中的10个国家落地实施。采集的专用数据涵盖软骨发育不全患者的发育里程碑、各类干预措施（如肢体延长手术、沃索肽与生长激素治疗）、并发症及健康相关生活质量，同时纳入标准人体测量学指标（如身高、体重等）。所有数据经伪匿名化处理后，提交至德国莱比锡大学医院的CrescNet中央数据库，按年龄与治疗状态开展分组分析。 研究结果：截至2025年5月，本研究共纳入来自32个三级医疗中心的486名受试者。最终对73名未接受治疗及186名经基因确诊为软骨发育不全且接受沃索肽治疗的受试者数据进行分析。在接受沃索肽治疗的受试者中，以未接受治疗的欧洲软骨发育不全人群为参照的平均身高标准差评分，在治疗启动后第1、2、3年较基线水平均出现显著升高（P≤0.0001）。 研究结论：本数据采集模块可有效助力真实世界数据的收集，从而深化对软骨发育不全自然病程及各类干预措施相关临床结局的认知。接受沃索肽治疗受试者的生长数据与临床试验结果及已发表的真实世界研究数据高度一致。目前更长随访周期的后续研究仍在进行中。