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 monosodium urate (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/methotrexate co-therapy. Methods Serial DECT scans were obtained during pegloticase (8 mg biweekly infusions)/oral methotrexate (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 Two patients underwent serial DECT. Patient 1 (44-year-old male) completed 52-weeks of pegloticase/methotrexate 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/methotrexate co-therapy. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03635957