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

Nicola Dalbeth; John Botson; Kenneth Saag; Ada Kumar; Lissa Padnick-Silver; Brian LaMoreaux; Fabio Becce

doi:10.1016/j.jbspin.2024.105715

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

Joint Bone Spine. 2024 Mar 4:105715. doi: 10.1016/j.jbspin.2024.105715. Online ahead of print.

Authors

Nicola Dalbeth¹, John Botson², Kenneth Saag³, Ada Kumar⁴, Lissa Padnick-Silver⁵, Brian LaMoreaux⁴, Fabio Becce⁶

Affiliations

¹ Department of Medicine, University of Auckland, M&HS Building 507, 28 Park Ave. Grafton, Auckland, 1023 New Zealand.
² Orthopedic Physicians Alaska, 3801 Lake Otis Parkway, Anchorage, AK 99508, United States.
³ University of Alabama at Birmingham, 2000 6(th) Ave. South, Floor 3, Birmingham, AL 35233, United States.
⁴ Horizon Therapeutics plc (now Amgen Inc.), 1 Horizon Way, Deerfield, IL 60015, United States.
⁵ Horizon Therapeutics plc (now Amgen Inc.), 1 Horizon Way, Deerfield, IL 60015, United States. Electronic address: Lsilve01@amgen.com.
⁶ Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, University of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland.

PMID: 38447697
DOI: 10.1016/j.jbspin.2024.105715

Abstract

Objective: Monosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase+MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored.

Methods: Patients received pegloticase (8mg every 2-weeks)+MTX (15mg/week orally) or pegloticase+placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Week 14, 24, and 52. Patients with paired baseline-Week52 images were included. Imaged regions with baseline MSU-crystal volume (V_MSU) <0.5cm³ were excluded to minimize artifact contributions. V_MSU and bone erosion remodeling were assessed.

Results: Eight patients (6 MTX, 2 PBO) were included. Included patients had received 52-weeks (5 MTX), 42-weeks (1 PBO), and 6-weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU <6mg/dL on allopurinol (n=2)/febuxostat (n=1). At Week52, V_MSU had markedly decreased in both the pegloticase+MTX and pegloticase+PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation.

Conclusion: Rapid V_MSU depletion pegloticase therapy was observed with concomitant bone remodeling within 1-year. Following pegloticase discontinuation, V_MSU reduction slowed or stopped even when SU was maintained <6mg/dL with oral ULT.

Clinical trial registration: NCT03994731.

Keywords: Gout; bone erosion; dual-energy computed tomography; imaging; methotrexate; pegloticase.

Associated data

ClinicalTrials.gov/NCT03994731