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
