Breakthrough Study Reveals Rapid Reduction of Gout-Related Crystal Deposits with Pegloticase Therapy

A new study found that Monosodium urate (MSU) crystal deposits, detectable with dual-energy CT (DECT), diminish rapidly during pegloticase treatment, particularly when co-administered with methotrexate (MTX) for uncontrolled gout. The volume of MSU crystals also slowed or stopped even when SU was maintained at <6mg/dL with oral ULT.

The study findings were published in the journal Joint Bone Spine.

Monosodium urate (MSU) crystal deposits can be observed and measured using dual-energy CT (DECT). Pegloticase effectively reduces serum urate (SU) levels in uncontrolled gout patients, often with methotrexate (MTX) co-therapy to enhance response and mitigate infusion reactions. However, limited literature exists on DECT imaging during pegloticase+MTX treatment. Hence, researchers conducted a study to address this gap by presenting DECT findings from a larger cohort in a randomized controlled trial, investigating bone erosion remodeling following MSU depletion with pegloticase therapy, and exploring the impact of treatment duration. During the MIRROR RCT trial, patients were administered either pegloticase (8mg every 2 weeks) along with methotrexate (MTX) orally at a dose of 15mg/week, or pegloticase with a placebo (PBO).

A subgroup underwent DECT imaging on Day 1 (the initial pegloticase infusion) and at Weeks 14, 24, and 52. Patients with paired baseline-Week 52 images were analyzed. Regions with baseline MSU-crystal volume (VMSU) <0.5cm3 were excluded to minimize artifact contributions. VMSU and bone erosion remodeling were evaluated.

Results:

• Out of the eight patients included (six on MTX, two on PBO), five on MTX had undergone pegloticase therapy for 52 weeks, one on PBO for 42 weeks, and two on MTX and one on PBO for 6 weeks each.
• Patients who discontinued pegloticase prematurely maintained serum urate (SU) levels <6mg/dL on allopurinol (n=2) or febuxostat (n=1).
• By Week 52, VMSU had significantly decreased in both the pegloticase+MTX and pegloticase+PBO groups, with a more rapid reduction observed during pegloticase treatment.
• Bone-erosion remodeling was noted in 29 out of 42 (69%) evaluated erosions, with 29 (69%) demonstrating a decrease in size, 4 (9.5%) exhibiting recortication, and 3 (7.1%) showing new bone formation.

Thus, the study concluded a swift reduction in monosodium urate (MSU) crystal volume (VMSU) during pegloticase therapy, accompanied by concurrent bone remodeling within a year. However, upon discontinuation of pegloticase, the rate of VMSU reduction decelerated or halted, despite maintaining serum urate (SU) levels below 6mg/dL with oral urate-lowering therapy (ULT).

Further reading: Examination of 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. Doi: https://doi.org/10.1016/j.jbspin.2024.105715