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.

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.