Heterotopic Ossification in Palovarotene-Treated and Untreated Individuals with Fibrodysplasia Ossificans Progressiva: Matched and Weighted Analyses
Author(s)
Al Mukaddam M1, Baujat G2, Cheung AM3, De Cunto C4, Hsiao EC5, Keen R6, Marden J7, Signorovitch J7, Boing E8, Marino R8, Strahs A8, Pignolo RJ9
1Departments of Orthopaedic Surgery and Medicine, The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, 2Département de Génétique, Hôpital Universitaire Necker-Enfants Malades, Institut IMAGINE, Université Paris Cité, Paris, France, 3Department of Medicine and Joint Department of Medical Imaging, University Health Network, University of Toronto, Toronto, ON, Canada, 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, UK, 7Analysis Group, Inc., Boston, MA, USA, 8Ipsen, Cambridge, MA, USA, 9Department of Medicine, Mayo Clinic, Rochester, MN, USA
Presentation Documents
OBJECTIVES: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, genetic disorder characterized by progressive heterotopic ossification (HO), leading to cumulative disability. Post hoc analyses of HO volume changes observed during the phase III MOVE trial (NCT03312634) versus a non‑interventional natural history study (NHS; NCT02322255) allow further evaluation of palovarotene for the treatment of FOP.
METHODS: Mean annualized HO volume changes assessed by low-dose whole-body computed tomography from baseline until last available assessment were compared for patients receiving palovarotene (MOVE) and patients who did not receive treatment beyond standard of care (NHS) using 2-sample t-tests. The analysis excluded patients who transitioned from the NHS to MOVE. Propensity score matching and weighting were conducted to adjust for baseline differences between the independent groups. Scores were estimated via multivariable logistic regression on baseline age, sex, age-adjusted baseline HO, baseline CAJIS, and time since last flare-up. Sensitivity analyses compared HO volume change with square-root values or with reductions in HO volume coded as zero.
RESULTS: Overall, 61 untreated individuals (mean follow-up: 25.8 months) and 58 patients receiving palovarotene (mean follow-up: 15.6 months) were included in the propensity score analyses; 39 were successfully matched with balanced baseline characteristics. A statistically significant difference in mean annualized HO volumes between matched untreated (24.1x103 [±45.3x103] mm3) and treated (5.6x103 [±20.7x103] mm3) individuals was observed (−18.5x103 [±8.0x103] mm3; p<0.05), equating to a 76.9% lower annualized HO volume increase in treated patients. Sensitivity analyses with varying specifications, including stabilized and unstabilized weights, square root transformation, and recoding HO volume reductions as zero, all yielded similar directions of effects with varying statistical significance.
CONCLUSIONS: Propensity score matched and weighted analyses revealed significantly lower annualized increases in HO volume in patients who received palovarotene treatment, supporting its potential as a therapeutic option in FOP.
Conference/Value in Health Info
Value in Health, Volume 26, Issue 6, S2 (June 2023)
Code
CO32
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Drugs, Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal)