TY - JOUR
T1 - Growth parameters in children with achondroplasia
T2 - A 7-year, prospective, multinational, observational study
AU - Savarirayan, Ravi
AU - Irving, Melita
AU - Harmatz, Paul
AU - Delgado, Borja
AU - Wilcox, William R.
AU - Philips, John
AU - Owen, Natalie
AU - Bacino, Carlos A.
AU - Tofts, Louise
AU - Charrow, Joel
AU - Polgreen, Lynda E.
AU - Hoover-Fong, Julie
AU - Arundel, Paul
AU - Ginebreda, Ignacio
AU - Saal, Howard M.
AU - Basel, Donald
AU - Font, Rosendo Ullot
AU - Ozono, Keiichi
AU - Bober, Michael B.
AU - Cormier-Daire, Valerie
AU - Le Quan Sang, Kim Hanh
AU - Baujat, Genevieve
AU - Alanay, Yasemin
AU - Rutsch, Frank
AU - Hoernschemeyer, Daniel
AU - Mohnike, Klaus
AU - Mochizuki, Hiroshi
AU - Tajima, Asako
AU - Kotani, Yumiko
AU - Weaver, David D.
AU - White, Klane K.
AU - Army, Clare
AU - Larrimore, Kevin
AU - Gregg, Keith
AU - Jeha, George
AU - Milligan, Claire
AU - Fisheleva, Elena
AU - Huntsman-Labed, Alice
AU - Day, Jonathan
N1 - Funding Information:
We thank the families who participated in this study. The study was funded by BioMarin Pharmaceutical Inc. Conceptualization: R.S. W.R.W. E.F. A.H.-L. J.D.; Data Curation: R.S. C.M. E.F. A.H.-L. J.D. C.A. G.J. E.F.; Formal Analysis: A.H.-L.; Funding Acquisition: J.D.; Investigation: R.S. L.T. M.I. W.R.W. C.A.B. J.H.-F. R.U.F. P.H. F.R. M.B.B. L.E.P. I.G. K.M. J.C. D.H. K.O. Y.A. P.A. Y.K. K.K.W. H.M.S. H.M. D.B.; Methodology: R.S. W.R.W. C.A. C.M. G.J. E.F. J.D.; Project Administration: C.M. E.F. G.J.; Resources: J.D.; Software: K.G. A.H.-L.; Supervision: R.S. E.F. J.D.; Validation: R.S. E.F. K.G. A.H.-L. J.D.; Visualization: R.S. E.F. K.G. A.H.-L. J.D.; Writing-original draft: R.S. J.D.; Writing-review and editing: R.S. M.I. P.H. B.D. W.R.W. J.P. C.A.B. L.T. J.C. J.H.-F. P.A. I.G. H.M.S. D.B. R.U.F. K.O. M.B.B. V.C.-D. K.-H.L.Q.S. Y.A. F.R. D.H. K.M. H.M. Y.K. D.D.W. K.K.W. C.A. K.L. K.G. G.J. C.M. E.F. A.H.-L. J.D. The Institutional Review Board or Independent Ethics Committee at each site approved the study protocol and documentation. The main Institutional Review Board was the Royal Children's Hospital Melbourne, Human Research and Ethics Committee, with study approval number HREC32148C. The study was conducted in accordance with the European Clinical Trial Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC, the relevant United States Code of Federal Regulations sections and/or other national and local regulations as applicable, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Harmonised Tripartite Guideline (Guideline for Good Clinical Practice), and the ethical principles established by the Declaration of Helsinki. Written informed consent from all participants legally authorized representative (parent or legal guardian) and child assent (as appropriate and if required) were obtained prior to enrolment in the study. All individual patient data was de-identified. All authors have signed ethics attestation statements that have been submitted to the editorial staff at Genetics in Medicine and are available on request.
Funding Information:
We thank the families who participated in this study. The study was funded by BioMarin Pharmaceutical Inc.
Funding Information:
All authors were investigators in this clinical trial except for C.A., K.L., K.G., G.J., C.M., E.F., A.H.-L., and J.D., who are employees of the funder (BioMarin). R.S. L.T., F.R., K.M., have received consulting fees and grants from BioMarin. M.I. and W.R.W. have received consulting fees from BioMarin. D.B. has received grants from BioMarin. J.C. has received honoraria from Genzyme, Applied Therapeutics, and CHIESI Farmaceutici S.p.A. P.A. has received honoraria from BioMarin. P.H. and C.B. have received consulting fees, honoraria and grants from BioMarin. J.H.F. has received consulting fees from BioMarin,Therachon AG and Ascendis, and grants from BioMarin. M.B. has received consulting fees and grants from BioMarin, Ascendis, Therachon, QED, Tyra Biosciences, and Alexion Pharmaceuticals, Inc, and grants from BioMarin, Ascendis, Therachon, QED, Medlife, SOBI, and Shire. K.K.W. has received consulting fees from BioMarin, grants from BioMarin, Ultragenyx, Pfizer, and Theracon, and royalties from UptoDate.com . L.P. has received consulting fees from BioMarin, Sanofi/Genzyme, and Therachon, and grants from Sanofi/Genzyme, Takeda/Shire, Pfizer, and SOBI. The other authors declare no conflict of interests.
Publisher Copyright:
© 2022 The Authors
PY - 2022/12
Y1 - 2022/12
N2 - Purpose: This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control. Methods: In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing. Results: A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants <1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants <1 year was –2.5 for girls and −3.2 for boys and decreased up to the age 5 years (−5.3 for girls; −4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged <1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward. Conclusion: This study represents one of the largest datasets of prospectively collected medical and longitudinal growth data in children with achondroplasia. It serves as a robust historical control to measure therapeutic interventions against and to further delineate the natural history of this condition.
AB - Purpose: This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control. Methods: In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing. Results: A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants <1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants <1 year was –2.5 for girls and −3.2 for boys and decreased up to the age 5 years (−5.3 for girls; −4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged <1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward. Conclusion: This study represents one of the largest datasets of prospectively collected medical and longitudinal growth data in children with achondroplasia. It serves as a robust historical control to measure therapeutic interventions against and to further delineate the natural history of this condition.
KW - Achondroplasia
KW - Annualized growth velocity
KW - Anthropometrics
KW - Observational
KW - Pediatrics
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U2 - 10.1016/j.gim.2022.08.015
DO - 10.1016/j.gim.2022.08.015
M3 - Article
C2 - 36107167
AN - SCOPUS:85138145646
SN - 1098-3600
VL - 24
SP - 2444
EP - 2452
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 12
ER -