Monosodium urate crystal depletion and bone erosion remodeling during pegloticase treatment in patients with uncontrolled gout: Exploratory dual-energy computed tomography findings from MIRROR RCT.

Autor: Dalbeth N; Department of Medicine, University of Auckland, M&HS Building 507, 28 Park Ave. Grafton, 1023 Auckland, New Zealand., Botson J; Orthopedic Physicians Alaska, 3801 Lake Otis Parkway, 99508 Anchorage, AK, United States., Saag K; University of Alabama at Birmingham, 2000 6th Ave. South, Floor 3, 35233 Birmingham, AL, United States., Kumar A; Horizon Therapeutics plc (now Amgen, Inc.), 1 Horizon Way, 60015 Deerfield, IL, United States., Padnick-Silver L; Horizon Therapeutics plc (now Amgen, Inc.), 1 Horizon Way, 60015 Deerfield, IL, United States. Electronic address: lsilve01@amgen.com., LaMoreaux B; Horizon Therapeutics plc (now Amgen, Inc.), 1 Horizon Way, 60015 Deerfield, IL, United States., Becce F; Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, University of Lausanne, rue du Bugnon 46, 1011 Lausanne, Switzerland.
Jazyk: angličtina
Zdroj: Joint bone spine [Joint Bone Spine] 2024 Jul; Vol. 91 (4), pp. 105715. Date of Electronic Publication: 2024 Mar 04.
DOI: 10.1016/j.jbspin.2024.105715
Abstrakt: Objective: Monosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase+MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored.
Methods: Patients received pegloticase (8mg every 2weeks)+MTX (15mg/week orally) or pegloticase+placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Weeks 14, 24, and 52. Patients with paired baseline-Week 52 images were included. Imaged regions with baseline MSU-crystal volume (V MSU )<0.5cm 3 were excluded to minimize artifact contributions. V MSU and bone-erosion remodeling were assessed.
Results: Eight patients (6 MTX, 2 PBO) were included. Included patients had received 52weeks (5 MTX), 42weeks (1 PBO), and 6weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU<6mg/dL on allopurinol (n=2)/febuxostat (n=1). At Week 52, V MSU had markedly decreased in both the pegloticase+MTX and pegloticase+PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation.
Conclusion: Rapid V MSU depletion during pegloticase therapy was observed with concomitant bone remodeling within 1year. Following pegloticase discontinuation, V MSU reduction slowed or stopped even when SU was maintained<6mg/dL with oral ULT.
Clinical Trial Registration: NCT03994731.
(Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: