DECT visualization of rapid monosodium urate depletion and bone erosion remodeling during pegloticase/methotrexate co-therapy
Nicola Dalbeth, Fabio Becce, John K Botson, Brian Lamoreaux, Lin Zhao, Ada Kumar
Horizon Therapeutics, Deerfield
Objectives: In patients with gout who no longer respond to or cannot tolerate oral urate lowering therapies, pegloticase (pegylated uricase) can rapidly lower serum urate (SU)1 and resolve ≥1 tophus in 70% and 28% of treatment responders and nonresponders, respectively.2 dual-energy computed tomography (DECT) can image monosodium urate (MSU) deposits, including detecting subclinical tophi, and assess MSU volumes. Bone erosions can be imaged with DECT, allowing for erosion monitoring and scoring. This report examines serial DECT findings in patients undergoing pegloticase/methotrexate co-therapy during an open-label clinical trial (mirror ol).
Methodology: Serial DECT images (somatom definition, siemens healthineers) were obtained over the full treatment period (up to 52 weeks) in patients undergoing pegloticase (8 mg biweekly infusions) with oral methotrexate (15 mg/week) co-therapy in the mirror-ol trial (nct03635957). Bilateral hand/wrist, elbow, foot/ankle, and knee images were obtained at a single center, post-processed using default settings, and interpreted by authors experienced in DECT interpretation (nd, fb, ak). MSU deposition and volume in each scan were assessed and bone erosions were identified (3 largest bone erosions in each joint evaluated for evidence of healing, defined as decreasing size, sclerosis, or new bone formation). The number of joints with MSU deposition on DECT were compared to the number of joints affected by tophi on clinical examination.
Findings: Two patients underwent serial DECT imaging. Patient 1 (44-year-old asian male) underwent 52 weeks of study therapy; patient 2 (51-year-old caucasian male) underwent 10 weeks of therapy (study treatment discontinued after therapeutic response was lost, table). At baseline, clinical examination identified 4 joints with tophi in patient 1 and 7 joints with tophi in patient 2 (figure 1). In contrast, DECT detected 73 joints with MSU deposition (total MSU volume: 128.76 cm3) and 55 joints with MSU deposition (total MSU volume: 59.20 cm3) in patients 1 and 2, respectively. At end of treatment, DECT scanning showed that both the number of joints with MSU deposition (patient 1: 0 joints, patient 2: 5 joints), and overall MSU volume (1.33 cm3 [99% reduction], 25.07 cm3 [58% reduction]) were markedly reduced (figure 2). Average MSU volume reduction per joint was 99±1% at 52 weeks in patient 1 and 63±18% at 10 weeks in patient 2, indicating relatively uniform MSU crystal debulking throughout the body. Both patients had at least one joint with evidence of bone erosion remodeling at the end of treatment, but no evaluated erosion had completely resolved (figure 2).
Significance: This study showed that DECT can identify up to 18-times more joints affected by MSU than by tophi on clinical examination, while also quantifying MSU deposition volume. Additionally, DECT demonstrated rapid MSU deposit resolution with evidence of bone erosion remodeling in both a clinical responder after 52 weeks of pegloticase plus methotrexate co-therapy (full study treatment course, 99% total MSU volume reduction) and a clinical nonresponder after 10 weeks of therapy (partial treatment course, 58% total MSU volume reduction).
References 1. Sundy JS, et al. Jama 2011;306:711-20. 2. Mandell BF, et al. Arthritis Res Ther 2018;20:286.