Pegloticase Use Could Contribute to Bone Remodeling in Gout Patients

An analysis of patient data from the MIRROR trial suggests use of pegloticase (Krystexxa) plus methotrexate could halt bone erosion in people with uncontrolled gout.

Presented at the European Congress of Rheumatology 2023 annual meeting, results of the study, which included dual-energy CT (DECT) data from 8 patients within the trial, suggest use of pegloticase plus methotrexate was associated with a rapid and near complete resolution of progressive monosodium rate crystal deposition volume after just 1 year of treatment, with investigators also highlighted signals of concomitant bone erosion remodeling with pegloticase plus methotrexate.¹

“The idea here is that if you effectively clear out all of those urate crystals, which are which what's causing the bone erosion and what's causing bone damage, the bone actually recognizes that something is wrong, and it can start to begin the process of healing,” said Brian LaMoreaux, MD, senior medical director of Horizon Therapeutics, in an interview HCPLive from EULAR 2023.

The MIRROR trial served as the basis for approval of the expanded indication of pegloticase for uncontrolled gout and, since being published in Arthritis & Rheumatology in September 2022, the trial has been used for a number of posthoc analyses, including an additional analysis at EULAR 2023 examining quality of life improvements with respecified patient-reported outcomes from within the trial.²

In the current study, investigators sought to examine the effects of pegloticase plus methotrexate relative to pegloticase plus placebo on monosodium rate crystal deposits. To be considered for inclusion in the analysis, patients needed to have DECT imaging available from baseline and week 52. From the trial, investigators identified 6 patients receiving pegloticase plus methotrexate and 2 patients receiving pegloticase plus placebo for inclusion in the study.¹

Upon analysis of DECT imaging, results suggested use of pegloticase plus methotrexate was associated with a rapid and near complete resolution of MSU crystal deposits within 1 year of initiating treatment, with a 94% volume reduction observed in 9 imaged regions of 6 patients who received pegloticase plus methotrexate and a 90% volume reduction in 5 imaged regions of 2 patients who received pegloticase plus placebo.¹

When assessing bone erosion, evidence of remodeling was observed in 69% of evaluated erosions. Among the erosions with remodeling, 100% had a decrease in size, with a mean change in volume of -7%. Further analysis suggested recortication was observed among 14% of these erosions and newborn formation was observed in 10% of the erosions with remodeling.¹

To learn more about how these results can help inform care of people with uncontrolled gout, our editorial team sat down with LaMoreaux while on-site in Milan for EULAR 2023.

Disclosures: Dr. LaMoreaux is a shareholder and employee of Horizon Therapeutics.

References:

1. Dalbeth N, Botson J, Saag K. Bone erosion remodeling after depletion of monosodium urate deposition with intensive urate-lowering with pegloticase in patients with uncontrolled gout: MIRROR RCT dual-energy CT findings. Paper presented at: European Congress of Rheumatology (EULAR) 2023. Milan, Italy. May 31 – June 3, 2023.
2. Campbell P. Pegloticase use and quality of life in uncontrolled gout, with Brian Lamoreaux, MD. HCP Live. June 1, 2023. Accessed June 2, 2023. https://www.hcplive.com/view/pegloticase-use-and-quality-of-life-in-uncontrolled-gout-with-brian-lamoreaux-md.