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 - 11/07/24
Highlights |
• | Dual-energy CT (DECT) can image and quantify urate deposition and bone erosions. |
• | Intensive urate-lowering with pegloticase led to rapid urate depletion on DECT. |
• | Deposited urate depletion was fastest during pegloticase treatment. |
• | With urate depletion, bone remodeling occurred within 1year in most erosions. |
Abstract |
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 (VMSU)<0.5cm3 were excluded to minimize artifact contributions. VMSU 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, VMSU 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 VMSU depletion during pegloticase therapy was observed with concomitant bone remodeling within 1year. Following pegloticase discontinuation, VMSU reduction slowed or stopped even when SU was maintained<6mg/dL with oral ULT.
Clinical trial registration |
NCT03994731.
Le texte complet de cet article est disponible en PDF.Keywords : Gout, Bone erosion, Pegloticase, Methotrexate, Imaging, Dual-energy computed tomography
Plan
Vol 91 - N° 4
Article 105715- juillet 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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