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, W1W 5AQ, United Kingdom., Dahir KM; Program for Metabolic Bone Disorders, Vanderbilt University Medical Center, Nashville, TN 37232, United States., McGinniss J; Medical Affairs, Scientific Communications, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, United States., Sanchez RJ; Medical Affairs, Scientific Communications, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, United States., Mellis S; Medical Affairs, Scientific Communications, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, United States., Economides AN; Medical Affairs, Scientific Communications, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, United States., Di Rocco M; Department of Pediatrics, Unit of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, 16147, Italy., Orcel P; Department of Rheumatology - DMU Locomotion, AP-HP Nord - Université de Paris and INSERM U1132 Bioscar, Paris, France., Roux C; Centre d'Evaluation des Maladies Osseuses, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, 27 Rue du Faubourg Saint-Jacques, Paris, 75014, France., Tabarkiewicz J; Centre for Innovative Research in Medical and Natural Sciences, Rzeszów University, Rzeszów, 35-310, Poland., Bachiller-Corral J; Department of Rheumatology, Hospital Universitario Ramón y Cajal, Madrid, 28034, Spain., Cheung AM; Department of Medicine and Joint Department of Medical Imaging, University Health Network, University of Toronto, Toronto, ON, M5S 1A1, 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 19104, United States., Mohammadi K; Medical Affairs, Scientific Communications, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, United States., Gu J; Medical Affairs, Scientific Communications, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, United States., Srinivasan D; Medical Affairs, Scientific Communications, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, United States., Trotter DG; Medical Affairs, Scientific Communications, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, 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, 1081 HV, 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 19104, United States., Pignolo RJ; Department of Medicine, Mayo Clinic, Rochester, MN 55905, 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 Sep 26; Vol. 39 (10), pp. 1486-1492.
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 wk over 28 wk (Period 1), followed by a 28-wk open-label treatment and extension (Periods 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 CT. Patient-reported flare-ups were defined by any 2 of the following: 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 vs those without (median [Q1:Q3] of 16.6 [12.0:31.1] vs 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] vs 48.0 [15.0:1.00] d) and the severity of flare-ups vs placebo. Frequency of corticosteroid use was numerically reduced in those treated with garetosmab (40.0%) vs placebo (58.3%). In this analysis, 71% of placebo-treated adults with FOP experienced flare-ups over 28 wk, 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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