Reliable detection and measurement of monosodium urate (MSU) crystal deposits in gout patients can be achieved with dual-energy computed tomography (DECT). Serial DECT imaging of 2 patients in the MIRROR open-label trial (pegloticase + oral methotrexate [MTX] co-treatment) revealed a quick and progressive reduction in MSU deposition volume during therapy. More people in the MIRROR RCT underwent serial DECT imaging throughout treatment, and the urate-lowering response rate to pegloticase was higher when it was co-administered with MTX (71.0% vs. 38.5% with monotherapy during Month 6). In this article, researchers presented the results of the MIRROR RCT about the serial deposition of DECT MSUs. Pegloticase (8 mg bimonthly infusions) plus blinded MTX (15 mg/wk) or placebo (PBO) was administered to participants in a randomized, controlled trial (NCT03635957) with a 2:1 allocation ratio. During the 52-week treatment period, serial pictures were acquired at DECT-enabled stations according to a defined acquisition technique (Day 1 [pegloticase infusion 1]; Wks 14, 24, 52). Images of both the right and left hands, elbows, feet, and knees were taken and processed with the default settings before being read by a central reader who was blinded to the therapy group and the patient’s response. Every scan was analyzed for the volume of MSU deposits. Analyses comprised patients who had both pre-treatment and Wk 52 pictures. To reduce the likelihood of significant contributions from artifacts introduced by DECT, researchers ruled out joints with a baseline MSU volume of less than 0.5 cm3 or below. Data from 6 MTX and 2 PBO patients was used for statistical purposes. After 52 weeks of pegloticase + MTX, 5 patients were considered to have responded to treatment by Month 6. The remaining patient (a nonresponder) stopped receiving pegloticase + MTX at week 6 and started taking allopurinol (keeping his serum uric acid levels < 6 mg/dL until week 52). In Month 6, after 42 weeks of pegloticase + PBO treatment, 1 patient showed signs of improvement. The remaining patient (a nonresponder) stopped receiving pegloticase + PBO at week 6 and started taking allopurinol (which kept his serum uric acid levels <6 mg/dL through week 52). Throughout the course of treatment, the MSU volume steadily and significantly declined in both groups (Wk 52, MTX: -93.8%  ± 8.8% across 9 imaging regions of 6 patients, PBO: -95.7% ±3.1% across 4 imaging regions of 2 patients). At week 52, the MSU volume changes for the 2 patients who received pegloticase plus MTX/PBO co-therapy for 6 weeks were -72.3% (MTX) and -97.1% (PBO). When comparing the 2 therapy groups, the volume reduction of MSUs was consistent across different anatomical locations in the same patient. Rapid debulking of MSU deposits across numerous joints was observed by DECT imaging following pegloticase + MTX/PBO co-therapy, with a mean urate volume reduction of 95% over 52 wks. The 2 patients who had previously been classified as nonresponders after 6 weeks of pegloticase saw significant weight loss after starting allopurinol simultaneously with the drug’s withdrawal from their system. These results add to the growing body of evidence that reducing urate levels with pegloticase reduces the MSU burden in joints.