Pegloticase Yields Complete Gout Remission in Post Hoc Analysis

Based on results from a post hoc analysis of the MIRROR trial, pegloticase, a recombinant pegylated uricase, may lead to complete remission in patients with gout who had been taking the medication for 52 weeks.

The MIRROR trial was a phase 4, multicenter, placebo-controlled, randomized clinical trial comparing the safety and efficacy of pegloticase administered with methotrexate (MTX) cotherapy versus pegloticase administered with placebo. All enrolled patients had uncontrolled gout, defined as elevated serum urate levels (≥7 mg/dL), oral ULT inefficacy or intolerance, and ongoing signs or symptoms of gout (≥2 flares in the year prior, ≥1 tophus, and/or chronic gouty arthritis). The presence of tophi was determined by central reader evaluation of photographs.1

“In this post hoc analysis, we used existing pegloticase clinical trial data from the Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase (MIRROR) RCT, which investigated gout remission through an adapted 6-criteria definition and an adapted, simplified 3-criteria definition recently proposed by G-CAN that would be more easily used in a clinical setting,” wrote Yael Klionsky, MD, Wake Forest University School of Medicine, and colleagues.1

Klionsky and colleagues utilized a 6-criterion definition of remission, which was determined through a series of Delphi consensus exercises conducted in 2016. At the time, the survey included 49 respondents, reaching a consensus for inclusion of serum urate, flares, tophi, pain, and patient global assessment of disease activity.2

Included patients were randomly assigned in a 2:1 ratio to either oral MTX (15 mg/week) or placebo as cotherapy to pegloticase (8 mg infusion every 2 weeks) for up to 52 weeks. An MTX tolerance assessment was conducted on each patient for 2 weeks before randomization. Patients also underwent a 4-week masked run-in of MTX or placebo before the first infusion on day 1.1

Investigators gave all participants a standard gout flare prophylaxis regiment for ≥1 week prior to day 1, and standard preinfusion prophylaxis, including fexofenadine, methylprednisolone, and acetaminophen, before each pegloticase infusion. Those with SU values >6 mg/dL at 2 consecutive scheduled visits starting at week 2 discontinued treatment.1

MIRROR had a primary efficacy endpoint of serum-lowering response rate, with secondary endpoints including the proportion of treatment responders during weeks 48-52, proportion of patients with tophi at baseline who had completed resolution of ≥1 tophus at week 52, and change from baseline in Health Assessment Questionnaire (HAQ) scores at week 52.1

A collective 145 patients were included in the study. Of these, 96 received pegloticase with MTX and 49 received pegloticase with placebo. A total of 90 patients remained on treatment through both week 24 and week 52, respectively. Investigators noted a mean age between patients of 54.8 (standard deviation [SD] 12.5) years and a mean history of gout of 14 (SD 10.7) years.1

At week 24, 13.3% of patients (12 of 90) had achieved gout remission. 43.2% achieved gout remission by the end of the study at week 52. Based on a simplified 3-criteria definition, 36.7% of patients and 70.3% of patients achieved remission at week 24 and 52, respectively. Most patients exhibited an improvement in most remission criteria by week 52.1

Investigators also found that a total of 98.9% of patients had a sustained SU level <6 mg/dL at week 25 and 98.6% at week 52. The proportion of patients meeting remission criteria increased progressively during treatment. The tophus criterion was the least frequently met, with 34% and 68.3% achieving the result at week 24 and 52, respectively. Most patients reported low gout-related pain (HAQ-Pain ≤1; 73% [54 of 74]), had a low disease burden (PhGA score: 74.3% [55 of 74]), and had not experienced a gout flare in the previous 3 months (89.2% [66 of 74]).1

“This demonstrates the vital importance of proper SU management, and not just flare and pain management, in patients with gout,” wrote Klionsky and colleagues. “Further, this study begins to demonstrate the usefulness of a standardized gout remission definition in defining a clear goal for therapy in both patients and physicians.”1

References

1. Klionsky Y, Torralba K.D, Obermeyer K, et al. Gout Remission With Pegloticase-Induced Intensive Urate-Lowering Therapy: A Post Hoc Clinical Trial Analysis. ACR Open Rheumatology, 7: e70080. https://doi.org/10.1002/acr2.70080

2. de Lautour H, Taylor WJ, Adebajo A, et al. Development of Preliminary Remission Criteria for Gout Using Delphi and 1000Minds Consensus Exercises. Arthritis Care Res (Hoboken). 2016;68(5):667-672. doi:10.1002/acr.22741