Characterization of flare-ups and impact of Garetosmab in adults with Fibrodysplasia Ossificans Progressiva: a post hoc analysis of the randomized, double-blind, placebo-controlled LUMINA-1 trial.

Autor: Keen R; Centre for Metabolic Bone Disease Royal National Orthopaedic Hospital NHS Trust, London, United Kingdom., Dahir KM; Program for Metabolic Bone Disorders, Vanderbilt University Medical Center, Nashville, TN, United States., McGinniss J; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States., Sanchez RJ; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States., Mellis S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States., Economides AN; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States., Di Rocco M; Department of Pediatrics, Unit of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Orcel P; AP-HP.Nord - Université de Paris and INSERM U1132 Bioscar, Paris, France., Roux C; Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France., Tabarkiewicz J; Rzeszów University, Rzeszów, Poland., Bachiller-Corral J; Hospital Universitario Ramón y Cajal, Madrid, Spain., Cheung AM; Department of Medicine and Joint Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Ontario, Canada., Al Mukaddam M; Departments of Orthopaedics, Medicine and the Center for Research in FOP & Related Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States., Mohammadi K; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States., Gu J; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States., Srinivasan D; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States., Trotter DG; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States., Eekhoff EMW; Department of Endocrinology and Metabolism, Amsterdam University Medical Centers (UMC), Vrije Universiteit, Amsterdam UMC Expert Center in Rare Bone Disease, Amsterdam Reproduction & Development, Amsterdam, Netherlands., Kaplan FS; Departments of Orthopaedics, Medicine and the Center for Research in FOP & Related Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States., Pignolo RJ; Department of Medicine, Mayo Clinic, Rochester, MN, United States.
Jazyk: angličtina
Zdroj: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2024 Aug 31. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1093/jbmr/zjae140
Abstrakt: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder, characterized by progressive heterotopic ossification (HO) and painful soft-tissue inflammatory flare-ups. This was a post-hoc analysis from a phase 2 (NCT03188666) trial in which adults with FOP received intravenous anti-activin A antibody garetosmab 10 mg/kg or placebo every 4 weeks over 28 weeks (Period 1), followed by a 28-week open-label treatment and extension (Period 2 and 3). Here we describe flare-ups, their relationship to new HO lesions, and the impact of garetosmab on flare-ups. Volume of new HO lesions was measured by computed tomography. Patient-reported flare-ups were defined by any two of: new onset of pain, swelling, joint stiffness, decrease in movement, or perceived presence of HO. Flare-ups were experienced by 71% (17/24) of placebo-treated patients, 59% (10/17) of whom developed a new HO lesion irrespective of flare-up location; 24% of flare-ups location-matched new HO lesions. Twenty-nine new HO lesions occurred in the placebo cohort by week 28, of which 12 (41%) occurred in the same location as new or ongoing flare-ups. A higher volume of newly formed heterotopic bone (week 28) occurred in placebo-treated patients who had experienced a prior flare-up versus those without (median [Q1:Q3] of 16.6 [12.0:31.1] cm3 versus 3.2 cm3). Garetosmab was previously shown to decrease patient-reported flare-up frequency in Period 1; here, garetosmab reduced the median (Q1:Q3) duration of patient reported flares (15.0 [6.0:82.0] versus 48.0 [15.0:1.00] days) and severity of flare-ups versus placebo. Frequency of corticosteroid use was numerically reduced in those treated with garetosmab (40.0%) versus placebo (58.3%). In this analysis, 71% of placebo-treated adults with FOP experienced flare-ups over 28 weeks, which were associated with an increased volume of newly formed heterotopic bone. Garetosmab reduced the severity and duration of flare-ups with effects sustained during the entire trial.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)
Databáze: MEDLINE
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