A Global Natural History Study of Fibrodysplasia Ossificans Progressiva (FOP): 12-Month Outcomes

M Al Mukaddam; C Stockklausner; RJ Pignolo; G Baujat; MA Brown; C De Cunto; M Di Rocco; EC Hsiao; R Keen; K-H Le Quan Sang; A Strahs; R Marino; FS Kaplan

doi:10.1055/s-0040-1722141

Osteologie, Inhaltsverzeichnis

Osteologie 2021; 30(01): 73
DOI: 10.1055/s-0040-1722141

2. Abstracts

A Global Natural History Study of Fibrodysplasia Ossificans Progressiva (FOP): 12-Month Outcomes

M Al Mukaddam

¹Departments of Orthopaedic Surgery & Medicine, University of Pennsylvania, Philadelphia, PA, USA, Perelman School of Medicine, The Center for Research in FOP and Related Disorders, Philadelphia

,

C Stockklausner

²Klinikum Garmisch-Partenkirchen, Akademisches Lehrkrankenhaus der Ludwig-Maximilians-Universität München (LMU), Kinder- und Jugendmedizin, Garmisch-Partenkirchen

,

RJ Pignolo

³Department of Medicine, Mayo Clinic, Rochester, Rochester, MN

,

G Baujat

⁴Département de Génétique, Institut IMAGINE, Hôpital Universitaire Necker-Enfants Malades, Paris, France, Paris

,

MA Brown

⁵King’s College London, Guy’s & St Thomas’ NHS Foundation Trust and King’s College London NIHR Biomedical Research Centre, London

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C De Cunto

⁶Pediatric Rheumatology SectionDepartment of Pediatrics, Hospital Italiano de Buenos Aires, Buenos Aires

,

M Di Rocco

⁷Unit of Rare Diseases, Department of Pediatrics, Giannina Gaslini Institute, Genoa, Genoa

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EC Hsiao

⁸7Division of Endocrinology and Metabolism, UCSF Metabolic Bone Clinic, Institute of Human Genetics, University of California-San Francisco, San Francisco, CA

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R Keen

⁹Royal National Orthopaedic Hospital, Stanmore, Centre for Metabolic Bone Disease, Stanmore

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K-H Le Quan Sang

⁴Département de Génétique, Institut IMAGINE, Hôpital Universitaire Necker-Enfants Malades, Paris, France, Paris

,

A Strahs

¹⁰Ipsen Pharma GmbH, Newton, MA

,

R Marino

¹⁰Ipsen Pharma GmbH, Newton, MA

,

FS Kaplan

¹¹Departments of Orthopaedic Surgery & Medicine, The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia, PA

› Institutsangaben

Abstract

Volltext

Introduction FOP is an ultra-rare, severely disabling genetic disorder characterized by cumulative heterotopic ossification (HO), often preceded by episodic flare-ups, leading to physical disability and early death. FOP is diagnosed and managed by multiple healthcare professionals, including bone specialists. Objective: A prospective, 36-month, global natural history study (NCT02322255) was designed to investigate the progression of FOP, HO, and impact on physical function. Results are described for the first 12 months.

Methods Individuals with FOP aged ≤65 years with documented ACVR1R206H mutation were eligible. HO volume was assessed by low-dose whole-body computed tomography (WBCT; excluding the head) interpreted at a blinded, central laboratory using pre-specified procedures. Physical function was evaluated using the Cumulative Analogue Joint Involvement Scale (CAJIS; total score 0–30 represents degree of ankylosis across 15 joints) and the FOP Physical Function Questionnaire (FOP-PFQ; % total score); higher scores indicate more severe limitations. Changes from Baseline (BL) in HO volume, CAJIS and FOP-PFQ at Month 12 were evaluated.

Results Of 114 participants with BL data, 99 (aged 4–56 years at enrollment, mean 17 years; 56 % male) had a Month 12 assessment and 93 had evaluable WBCT HO data at BL and Month 12. Over 12 months, 40 % (37/93) developed new HO and 48 % (48/99) reported ≥1 flare-up. Of participants with new HO, 65 % (24/37) reported ≥1 flare-up (mean 2.3 flare-ups/year) and 35 % (13/37) reported no flare-up. Of participants with no new HO, 43 % (24/56) reported ≥1 flare-up (mean 1.8 flare-ups/year). Among all participants, mean new HO volume in those who reported flare-ups was 39,718 mm3 (SD: 91,969 mm3; n = 48) vs 5,081 mm3 (SD: 14,582 mm3; n = 45) in those who did not. Mean changes from BL in CAJIS and FOP-PFQ were minimal (CAJIS: 0.6 [SD: 2.4; median: 1.0; n = 99]; FOP-PFQ: 4.4 % [SD: 11.2 %; median: 3.7 %; n = 90]) and similar across participants with or without new HO.

Discussion In participants with FOP, WBCT HO volume increased over 12 months. Among those who experienced new HO, this was not preceded by a flare-up in over one third of cases. Among all participants, mean new HO volume in those who reported flare-ups was ~8 times higher than in those who did not. CAJIS and FOP PFQ were not sufficiently sensitive to assess FOP disease progression over 12 months. Measuring HO may be a viable way to monitor changes in FOP over short periods of time.

Keywords FOP, NHS, rare bone disease

Korrespondenzadresse Mona Al Mukaddam, Departments of Orthopaedic Surgery & Medicine, University of Pennsylvania, Philadelphia, PA, USA, Perelman School of Medicine, The Center for Research in FOP and Related Disorders, 3737 Market Street, 19104 Philadelphia, USA

E-Mail lisa.katharina.wagner@ipsen.com

Conflict of interest Research investigator: Clementia/Ipsen, Regeneron; Non-paid consultant: Biocryst, Blueprint, Daiichi Sankyo, Keros; Advisory board (all voluntary): IFOPA registry Medical Advisory Board, International Clinical Council on FOP