ESPE2021 Henning Andersen Prize Winners A Global Natural History Study of Fibrodysplasia Ossificans Progressiva (FOP): 36-Month Outcomes in Participants Aged <25 Years (1 abstracts)
A Global Natural History Study of Fibrodysplasia Ossificans Progressiva (FOP): 36-Month Outcomes in Participants Aged <25 Years
Robert J. Pignolo 1 , Geneviève Baujat 2 , Matthew A. Brown 3 , Carmen L. De Cunto 4 , Edward C. Hsiao 5 , Richard Keen 6 , Mona Al Mukaddam 7 , Kim-Hanh Le Quan Sang 8 , Rose Marino 9 , Aude Houchard 10 & Frederick S. Kaplan 7
1Department of Medicine, Mayo Clinic, Rochester, MN, USA.;2Département de Génétique, Institut IMAGINE and Hôpital Universitaire Necker-Enfants Malades, Paris, France.;3Guy’s and St Thomas’ NHS Foundation Trust and King’s College London NIHR Biomedical Research Centre, London, United Kingdom.;4Pediatric Rheumatology Section, Department of Pediatrics, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.;5Division of Endocrinology and Metabolism, the UCSF Metabolic Bone Clinic, the Institute of Human Genetics, and the UCSF Program in Craniofacial Biology, Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.;6Centre for Metabolic Bone Disease, Royal National Orthopaedic Hospital, Stanmore, United Kingdom.;7Departments of Orthopaedic Surgery and Medicine, The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.;8Département de Génétique, Institut IMAGINE and Hôpital Universitaire Necker-Enfants Malades, Pairs, France.;9Ipsen, Newton, MA, USA.;10Ipsen, Boulogne-Billancourt, France
Background: FOP is an ultra-rare, severely disabling genetic disorder characterised by progressive heterotopic ossification (HO) following flare-ups. The median age at diagnosis is 5 years, and patients are managed by multiple specialties. No study to date has provided a longitudinal evaluation of FOP. Final data are presented for participants, aged <25 years, enrolled in the first 36-month, prospective, global natural history study of FOP (NCT02322255).
Methods: Individuals with FOP aged ≤65 years with a documented ACVR1R206H mutation were enrolled in the study; this analysis includes participants aged <25 years at Baseline. HO volume was evaluated by low-dose whole-body computed tomography (WBCT), excluding the head. Physical function was assessed using the Cumulative Analogue Joint Involvement Scale (CAJIS; total score 0-30 represents degree of ankylosis across joints) and the FOP Physical Function Questionnaire (FOP-PFQ; % total score); in both measures higher scores indicate more severe limitations. Change from Baseline (CfB) at Month 36 in HO volume, CAJIS and FOP-PFQ are presented.
Results: Of 87 participants aged <25 years at Baseline, 32 had evaluable WBCT HO data at Baseline and Month 36. At Month 36, 87.5% of participants had new HO. CfB in mean [SD] total WBCT HO volume over 36-months was highest in those aged 8-<15 years (88.28×103 [109.77×103] mm3; n = 13) and 15-<25 years (92.48×103 [164.12×103] mm3; n = 12) versus those 2-<8 years (52.54×103 [39.98×103] mm3; n = 7). Mean (SD) number of body regions with new HO at Month 36 were: 2-<8 years, 3.6 (2.6); 8-<15 years, 2.9 (1.7); 15-<25 years, 2.5 (2.0). Across median follow-up durations of 34.0 months, 30.1 months and 24.0 months for those aged 2-<8 years, 8-<15 years and 15-<25 years, mean (SD) number of clinical visit/telephone contact flare-ups by participant were 3.2 (3.2), 2.1 (2.1) and 1.7 (1.8), respectively. Mean (SD) number of flare-ups per participant-month were 0.1 (0.1), 0.1 (0.2) and 0.1 (0.1), respectively. Mean CfB to Month 36 in CAJIS and FOP-PFQ were small across age groups (CAJIS: 0.9-1.6 [n = 34]; FOP-PFQ: 2.4%-10.3% [n = 29]).
Conclusions: Total WBCT HO volume increased over 36-months confirming the progressive nature of FOP. Participants aged 2-<8 years reported the highest mean number of flare-ups and had more body regions with new HO versus participants 8-<25 years, despite lower new HO volumes. Measurement of new HO by WBCT is a viable method to monitor disease progression. CAJIS and FOP-PFQ were not sufficiently sensitive to assess progression over 36-months.
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