Study Shows Pegloticase Plus Methotrexate Improves Quality of Life in Gout Patients

Brian LaMoreaux, MD, MS
Credit: Horizon Therapeutics

An analysis of data from the MIRROR trial suggests use of pegloticase (Krystexxa) was associated with improved quality of life and clinical symptoms among patients with uncontrolled gout.

Presented at the European Congress of Rheumatology (EULAR) 2023 annual meeting, results of the study, which reported on prespecified patient-reported outcomes from the pivotal trial, suggests use of methotrexate was associated with a clinically meaningful improvement in quality of life, with even greater improvements observed in Health Assessment Questionnaire (HAQ) indices when co-treated methotrexate.

“Rheumatic disease is all about the patient's experience. We certainly check for synovitis and tophi, and we care about flares—gout flares especially,” said Brian LaMoreaux, MD, MS, senior medical director with Horizon Therapeutics, in an interview with HCPLive. “But there's all these other things that matter a ton to the patients that don't always wind up in, you know, a product label or prescribing information.”

Used as the basis for the US Food and Drug administration’s approval of the supplemental Biologics License Application for pegloticase injection for coadministration with methotrexate, the MIRROR trial has been the subject of multiple potshot analyses since results were initially published in Arthritis & Rheumatology in September 2022.² A 12-month, randomized, double-blind, placebo-controlled trial, the MIRROR trial enrolled 152 patients with uncontrolled gout and randomized them in a 2:1 ratio to pegloticase plus methotrexate and pegloticase plus placebo.³

The trial randomized a cohort of 152 participants, with 100 receiving pegloticase plus methotrexate and 52 receiving pegloticase plus placebo. The primary endpoint of the trial was the proportion of serum uric acid (sUA) responders, which investigators defined as an sUA less than 6 mg/dL for at least 80% of the time during weeks 20-24. Upon analysis, results of the trial suggested use of pegloticase plus methotrexate was associated with a greater than 30 percentage-point increase in response rate during weeks 20-24, with 71% of those receiving pegloticase plus methotrexate achieving the primary endpoint compared to just 39% of the pegloticase plus placebo group (P < .0001).

In the EULAR 2023 study, investigators took aim at developing a better understanding of the impact of pegloticase plus methotrexate on quality of life among patients with uncontrolled gout from within the trial. To do so, investigators designed their study as an analysis of prespecified patient-reported outcomes (PROs) as well as gout-related clinical measures recorded as part of the MIRROR trial.¹

PROs used in the MIRROR trial were various Health Assessment Questionnaire (HAQ) indices, including indices for pain, disability, and health. Gout-related clinical measures used in the trial were Physician Global Assessment of Gout (PhGA) and tender or swollen joint counts.v

Results of the analysis indicated all HAQ measures improved progressively throughout the study. When examining individual HAQ indices, results suggested the between-group difference at week 52 for disability did not achieve statical significance, but improvements were observed for both the pain and health indices after 52 weeks of therapy. When assessing gout-related clinical outcomes, results suggested those using pegloticase plus methotrexate was associated with marked reductions in tender and swollen joint counts at week 52.¹

“I think these are important because they really round out the patient experience. A gout patient is truly much, much more than their uric acid level or visible tophi in their elbow, their foot, or somewhere else,” LaMoreaux added. “This is the lived experience of those gout patients. And so, you know, having that data just like we did in the phase three studies and getting it out there. It helps clinicians and patients to understand what are the true benefits of this medicine, even if it's not in that prescribing information.”

References:

1. Botson J, Obermeyer K, LaMoreaux B, et al. QUALITY OF LIFE AND CLINICAL GOUT ASSESSMENT CHANGES IN UNCONTROLLED GOUT PATIENTS UNDERGOING PEGLOTICASE THERAPY AS PART OF THE MIRROR RANDOMIZED CONTROLLED TRIAL. Paper presented at: European Congress of Rheumatology (EULAR) 2023. Milan, Italy. May 31 – June 3, 2023.
2. Pine L. FDA approves pegloticase injection plus methotrexate for patients with uncontrolled gout. HCP Live. July 8, 2022. Accessed June 1, 2023. https://www.hcplive.com/view/fda-approves-pegloticase-injection-plus-methotrexate-for-patients-with-uncontrolled-gout.
3. Pine L. Pegloticase injection plus methotrexate significantly increases response rate in patients with gout. HCP Live. September 15, 2022. Accessed June 1, 2023. https://www.hcplive.com/view/pegloticase-injection-plus-methotrexate-significantly-increases-response-rate-in-patients-with-gout.