ECE2020 Audio ePoster Presentations Hot topics (including COVID-19) (110 abstracts)
A global natural history study of Fibrodysplasia Ossificans Progressiva (FOP): 12-month outcomes
Mona Al Mukaddam 1 , Robert J. Pignolo 2 , Geneviève Baujat 3 , Matthew A Brown 4 , Carmen De Cunto 5 , Maja Di Rocco 6 , Edward C. Hsiao 7 , Richard Keen 8 , Kim-Hanh Le Quan Sang 3 , Andrew Strahs 9 , Rose Marino 9 & Frederick S. Kaplan 1
1Departments of Orthopaedic Surgery & Medicine, The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; 2Department of Medicine, Mayo Clinic, Rochester, MN, United States; 3Département de Génétique, Institut IMAGINE and Hôpital Universitaire Necker-Enfants Malades, Paris, France; 4Guy’s & St Thomas’ NHS Foundation Trust and King’s College London NIHR Biomedical Research Centre, London, United Kingdom; 5Pediatric Rheumatology Section, Department of Pediatrics, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 6Unit of Rare Diseases, Department of Pediatrics, Giannina Gaslini Institute, Genoa, Italy; 7Division of Endocrinology and Metabolism, UCSF Metabolic Bone Clinic, Institute of Human Genetics, and UCSF Program in Craniofacial Biology, Department of Medicine, University of California-San Francisco, San Francisco, CA, United States; 8Centre for Metabolic Bone Disease, Royal National Orthopaedic Hospital, Stanmore, United Kingdom; 9Ipsen, Newton, MA, United States
Background: FOP is an ultra-rare, severely disabling genetic disorder characterised by cumulative heterotopic ossification (HO), often preceded by episodic flare-ups, leading to physical disability and early death. Initial misdiagnosis can occur in ~90% of individuals leading to unnecessary, often harmful interventions. FOP is diagnosed and managed by multiple specialists, including endocrinologists.
Objective: A prospective, 36-month, global natural history study (NCT02322255) was designed to investigate 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 ACVR1R206Hmutation 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 in HO volume, CAJIS and FOP‑PFQ at Month 12 were evaluated.
Results: Of 114 participants with Baseline data, 99 (aged 4–56 years at enrolment, mean 17 years; 56% male) had a Month 12 assessment and 93 had evaluable WBCT HO data at Baseline 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 (
Conclusions: 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 FOPPFQ were not sufficiently sensitive to assess disease progression over 12 months. Measuring HO may be a viable way to monitor changes in FOP over short periods of time.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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