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. 2024 Sep 17;19(1):347.
doi: 10.1186/s13023-024-03236-4.

International expert opinion on the considerations for combining vosoritide and limb surgery: a modified delphi study

Silvio Boero  1 , Julia Vodopiutz  2   3 , Mohamad Maghnie  4   5 , Josep M de Bergua  6 , Ignacio Ginebreda  7 , Hiroshi Kitoh  8 , Micha Langendörfer  9 , Antonio Leiva-Gea  10 , Jason Malone  11 , Philip McClure  12 , Gabriel T Mindler  13   14 , Dmitry Popkov  15 , Robert Rodl  16 , Pablo Rosselli  17 , Fabio Verdoni  18 , Viktor Vilenskii  19 , Aaron J Huser  20
Affiliations

International expert opinion on the considerations for combining vosoritide and limb surgery: a modified delphi study

Silvio Boero et al. Orphanet J Rare Dis. .

Abstract

Background: Achondroplasia is the most common form of skeletal disorder with disproportionate short stature. Vosoritide is the first disease-specific, precision pharmacotherapy to increase growth velocity in children with achondroplasia. Limb surgery is a standard approach to increase height and arm span, improve proportionality and functionality, as well as correcting deformities. The aim of this study was to gain expert opinion on the combined use of vosoritide and limb surgery in children and adolescents with achondroplasia.

Methods: An international expert panel of 17 clinicians and orthopaedic surgeons was convened, and a modified Delphi process undertaken. The panel reviewed 120 statements for wording, removed any unnecessary statements, and added any that they felt were missing. There were 26 statements identified as facts that were not included in subsequent rounds of voting. A total of 97 statements were rated on a ten-point scale where 1 was 'Completely disagree' and 10 'Completely agree'. A score of ≥ 7 was identified as agreement, and ≤ 4 as disagreement. All experts who scored a statement ≤ 4 were invited to provide comments.

Results: There was 100% agreement with several statements including, "Achieve a target height, arm span or upper limb length to improve daily activities" (mean level of agreement [LoA] 9.47, range 8-10), the "Involvement of a multidisciplinary team in a specialist centre to follow up the patient" (mean LoA 9.67, range 7-10), "Planning a treatment strategy based on age and pubertal stage" (mean LoA 9.60, range 8-10), and "Identification of short- and long-term goals, based on individualised treatment planning" (mean LoA 9.27, range 7-10), among others. The sequence of a combined approach and potential impact on the physes caused disagreement, largely due to a lack of available data.

Conclusions: It is clear from the range of responses that this modified Delphi process is only the beginning of new considerations, now that a medical therapy for achondroplasia is available. Until data on a combined treatment approach are available, sharing expert opinion is a vital way of providing support and guidance to the clinical community.

Keywords: Achondroplasia; Bone lengthening; Deformity correction; Limb surgery; Management; Modified Delphi process; Vosoritide.

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Conflict of interest statement

In addition to the individual disclosures outlined below, all authors with the exception of Jason Malone, Philip McClure, and Aaron Huser, participated in the expert group meetings, sponsored and organised by BioMarin Pharmaceutical Inc, from which the Delphi statements were developed. SB has received payment or honoraria, support for attending meetings and/or travel, and has participated on a Data Safety Monitoring Board or Advisory Board from BioMarin. JV has received payment or honoraria from BioMarin. MM has received grants or contracts from Pfizer, Novo Nordisk, and Merck Serono (paid to IRCCS Istituto Giannina Gaslini and DINOGM); Consulting fees and payment or honoraria from Merck Serono, Novo Nordisk, Pfizer, Sandoz, and BioMarin; and has participated on a Data Safety Monitoring Board or Advisory Board from Pfizer, Merck, Novo Nordisk and BioMarin. JBD has received payment or honoraria from BioMarin. IG has received payment for expert testimony, support for attending meetings and/or travel, has participated on a Data Safety Monitoring Board or Advisory Board and has a leadership or fiduciary role, all paid to his institution. HK has no conflicts of interest to declare. ML has received grants or contracts and consultancy fees from Smith Nephew, Nuvasive, and Stryker. ALG has received payment or honoraria, and support for attending meetings and/or travel from MBA-Orthofix and BioMarin. JM has no conflict of interest to declare. PM has received consultancy fees from Orthofix, Novasure, Wishbone, Novadip, Synthes and Smith/Nephew. GTM has received consulting fees from Kyowa Kirin and BioMarin; payment or honoraria from Kyowa Kirin and has participated on a Data Safety Monitoring Board or Advisory Board for BioMarin and Kyowa Kirin. DP has no conflicts of interest to declare. RR has received royalties from Merete, payment, or honoraria from Nuvasive, Smith Nephew, Infectopharm, FOMF, VKO and Kyowa Kirin; patents planned, issued, or pending with Merete and has participated on a Data Safety Monitoring Board or Advisory Board for Kyowa Kirin and BioMarin. PR has received payment or honoraria, support for attending meetings and/or travel, and has participated on a Data Safety Monitoring Board or Advisory Board for BioMarin. FV has received payment or honoraria from BioMarin, and has participated on a Data Safety Monitoring Board or Advisory Board for Biomedical Pharma. VV has no conflicts of interest to declare. AJH has received payments for speaker bureaus, and has participated on a Data Safety Monitoring Board or Advisory Board, from BioMarin.

Figures

Fig. 1
Fig. 1
Study design
See this image and copyright information in PMC

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