Dual-energy CT assessment of rapid monosodium urate depletion and bone erosion remodelling during pegloticase plus methotrexate co-therapy

Abstract

Objectives: Pegloticase rapidly lowers serum urate in uncontrolled/refractory gout patients, with ≥1 tophus resolution in 70% of pegloticase responders and 28% of non-responders. Dual-energy computed tomography (DECT) non-invasively detects MSU deposition, including subclinical deposition, quantifies MSU volumes and depicts bone erosions. This report presents DECT findings in MIRROR open-label trial participants receiving pegloticase+MTX co-therapy.

Methods: Serial DECT scans were obtained during pegloticase (8 mg biweekly infusions)+oral MTX (15 mg/week) co-therapy. Bilateral hand/wrist, elbow, foot/ankle and knee images were analysed with default post-processing settings. MSU volumes were quantified and bone erosions were identified and evaluated for remodelling (decreased size, sclerosis, new bone formation). DECT and physical examination findings were compared.

Results: 2 patients underwent serial DECT. Patient 1 (44-year-old male) completed 52 weeks of pegloticase+MTX co-therapy (26 infusions). Baseline examination detected 4 tophus-affected joints while DECT identified 73 MSU-affected joints (total MSU volume: 128.76 cm3). At end-of-treatment, there were no clinically-affected joints and 4 joints with DECT-detected MSU deposition. MSU volume decreased by 99% and bone erosion remodelling was evident. Patient 2 (51-year-old male) had 10 weeks of therapy (5 infusions), discontinuing because of urate-lowering response loss. Baseline examination detected 7 tophus-affected joints while DECT identified 55 MSU-affected joints (total MSU volume: 59.20 cm3). At end-of-treatment, there were 5 clinically affected joints and 42 joints with DECT-detected MSU deposition. MSU volume decreased by 58% and bone erosion remodelling was evident.

Conclusion: DECT detected subclinical MSU deposition and quantified changes over time. Rapid tophus resolution and bone erosion remodelling occurred during pegloticase+MTX co-therapy.

Trial registration: ClinicalTrials.gov, https://ichgcp.net/clinical-trials-registry/NCT03635957" title="See in ClinicalTrials.gov">NCT03635957.

Keywords: bone erosion; dual-energy CT; gout; monosodium urate deposition; pegloticase; tophus.

© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig. 1

Serial DECT imaging of the right foot/ankle of Patient 1 (A) and Patient 2 (B) MSU deposition is depicted in green. Patient 2 prematurely discontinued therapy due to loss of urate-lowering effect. Patients 1 and 2 had a total MSU volume reduction of 99% and 58% during therapy, respectively, and first metatarsal head bone erosion (Patient 1) and fifth metatarsal bone erosion (Patient 2) remodelling (decreased erosion size, increased sclerosis or new bone formation) was evident (arrows). Other joints also showed MSU volume reduction and bone erosion remodelling during therapy (C), with MSU reduction/joint averaging 99%±1% and 63%±18% in Patients 1 and 2, respectively. DECT, dual-energy computed tomography; MSU, monosodium urate.