Plenary Poster 30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2020

A global natural history study of fibrodysplasia ossificans progressiva (FOP): 12-month outcomes (#19)

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 , Shane Patella 10
  1. Departments of Orthopaedic Surgery & Medicine, The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  2. Department of Medicine, Mayo Clinic, Rochester, MN, USA
  3. Département de Génétique, Institut IMAGINE and Hôpital Necker-Enfants Malades, Paris, France
  4. Guy’s & St. Thomas’ NHS Foundation Trust and King’s College London , NIHR Biomedical Research Centre, London, UK
  5. Pediatric Rheumatology Section, Department of Pediatrics, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
  6. Unit of Rare Diseases, Department of Pediatrics, Giannina Gaslini Institute, Genoa, Italy
  7. Division 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, USA
  8. Centre for Metabolic Bone Disease, Royal National Orthopaedic Hospital, Stanmore, UK
  9. Ipsen, Newton, MA, USA
  10. Ipsen, Glen Waverley, VIC, Australia

Background: FOP is an ultra-rare genetic disorder characterized by cumulative heterotopic ossification ([HO]; often preceded by episodic flare-ups), leading to physical disability and shortened life expectancy. FOP is diagnosed and managed by multiple healthcare professionals.

 

Objective: A prospective, 36-month, global natural history study (NCT02322255) was designed to investigate FOP progression, HO, and impact on physical function. Here, we report 12-month outcomes.

 

Methods: Individuals with FOP aged ≤65years with documented ACVR1R206H mutation were eligible. HO volume was assessed by low-dose whole-body computed tomography (WBCT). Physical function was evaluated using Cumulative Analogue Joint Involvement Scale (CAJIS) and FOP Physical Function Questionnaire (FOP-PFQ). Changes from Baseline (CfB) in HO volume, CAJIS and FOP‑PFQ at Month 12 were evaluated.

 

Results: Of 114 participants with Baseline data, 99 (aged 4–56years, mean 17years; 56% male) had a Month 12 assessment; 93 had evaluable Baseline and Month 12 data. Over 12-months, 40% developed new HO; 48% reported ≥1 flare-up. Of participants with new HO, 65% reported ≥1 flare-up (mean 2.3/year); 35% reported no flare-up. Of participants without new HO, 43% reported ≥1 flare-up (mean 1.8/year). Across participants, mean (SD) new HO volume in those reporting flare-ups was 39,718 (91,969) mm3 (n=48) vs 5,081 (14,582) mm3 (n=45) in those who did not. Mean CfB in CAJIS and FOP-PFQ were minimal and similar across participants with/without new HO.

 

Conclusions: Among participants, HO volume increased over 12-months. In those with new HO, this was not preceded by flare-ups in over one third of cases. Across all participants, mean new HO volume in those reporting flare-ups was ~8 times higher than in those who did not. CAJIS and FOP-PFQ were not sufficiently sensitive to assess disease progression over 12-months. New HO volume can be used to measure FOP disease progression over the course of a clinical trial.