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
Nicola Dalbeth, John K. Botson, Kenneth G. Saag, Ada Kumar, Lissa Padnick‐Silver, Brian LaMoreaux, Fabio Becce
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 2-weeks)+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 Week 14, 24, and 52. Patients with paired baseline-Week52 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 52-weeks (5 MTX), 42-weeks (1 PBO), and 6-weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU <6mg/dL on allopurinol (n=2)/febuxostat (n=1). At Week52, 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 pegloticase therapy was observed with concomitant bone remodeling within 1-year. Following pegloticase discontinuation, VMSU reduction slowed or stopped even when SU was maintained <6mg/dL with oral ULT. Clinical trial registration: NCT03994731