Literature review and expert opinion on the impact of achondroplasia on medical complications and health-related quality of life and expectations for long-term impact of vosoritide: a modified Delphi study

Ravi Savarirayan, Wagner Baratela, Thomas Butt, Valérie Cormier-Daire, Melita Irving, Bradley S. Miller, Klaus Mohnike, Keiichi Ozono, Ron Rosenfeld, Angelo Selicorni, Dominic Thompson, Klane K. White, Michael Wright, Svein O. Fredwall

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: Achondroplasia is associated with disproportionate short stature and significant and potentially severe medical complications. Vosoritide is the first medicine to treat the underlying cause of achondroplasia and data from phase 3 and phase 2 extension studies showed effects on growth and body proportions. However, there are currently no long-term data available on the direct impact on endpoints such as medical complications and health-related quality of life (HRQoL). This study explored the perceived impact of achondroplasia on medical complications, HRQoL, healthcare resource use and mortality, and potential modifying effects of vosoritide, based on published evidence and expert opinion. Structured expert opinion was obtained by an international modified Delphi study among 14 experts in managing achondroplasia performed on a virtual platform and consisting of an explorative phase followed by an anonymous individual rating round. Results: Overall, the panelists expect that in individuals starting long-term treatment between 2 years of age and puberty, growth velocity increases observed in the clinical trials will be maintained until final height is reached (92% agreement) and will likely result in clinically meaningful improvements in upper-to-lower body segment ratio (85%). Earlier treatment initiation will likely result in a greater final height (100%) and more likely improve proportionality (92%) than later treatment. Although current data are limited, ≥ 75% of panelists find it conceivable that the earlier long-term treatment is started, the greater the probability of a positive effect on the lifetime incidence of symptomatic spinal stenosis, kyphosis, obstructive sleep apnea, and foramen magnum stenosis. These are among the most clinically important complications of achondroplasia because of their high impact on comorbidity, mortality, and/or HRQoL. A positive effect of vosoritide on the incidence of surgeries through lifetime was considered more likely with earlier long-term treatment (90%). Conclusions: This explorative study, based on international expert opinion, provides further insight into the medical and functional impacts of achondroplasia and how these might be modified through long-term use of vosoritide. The results can be used to guide the direction and design of future research to validate the assumptions and to discuss potential treatment outcomes with disease modifying therapies with families and clinicians.

Original languageEnglish (US)
Article number224
JournalOrphanet Journal of Rare Diseases
Volume17
Issue number1
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
The authors thank Dr. Michael Bober for his contribution as a panel member to the modified Delphi study and Swati Mukherjee (BioMarin International Ltd) and Wayne Pan (former BioMarin employee) for their help with the study design. The authors are also grateful to Ismar Healthcare NV for their assistance in the design, conduct and interpretation of data of the modified Delphi study and the writing of this manuscript, which were funded by BioMarin Pharmaceutical Inc., Novato, CA, USA.

Publisher Copyright:
© 2022, The Author(s).

Keywords

  • Achondroplasia
  • Activities of daily living
  • Complications
  • Delphi technique
  • Expert opinion
  • Growth
  • Health-related quality of life
  • Vosoritide

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