Kidney Week

Abstract: PUB314

Baseline Renal Characteristics and Trial Design for MIRROR RCT, Randomized Trial of Pegloticase with or Without Methotrexate for Uncontrolled Gout

Session Information

• Publication Only

Category: CKD (Non-Dialysis)

• 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Botson, John K., Orthopedic Physicians Alaska, Anchorage, Alaska, United States

John K. Botson,

• Parikh, Naval G., Napa Research Center, Pompano Beach, Florida, United States

Naval G. Parikh,

• Ong, Stephen, MD Medical Research, Oxon Hill, Maryland, United States

Stephen Ong,

• La, Dan T., Medvin Clinical Research, Tujunga, California, United States

Dan T. La,

• Locicero, Karon, GCP Clinical Research, Tampa, Florida, United States

Karon Locicero,

• Peterson, Jeff R., Western Washington Arthritis Clinic, Bothell, Washington, United States

Jeff R. Peterson,

• Grewal, Suneet, East Bay Rheumatology Medical Group, Inc., San Leandro, California, United States

Suneet Grewal,

• Peloso, Paul M., Horizon Therapeutics plc, Deerfield, Illinois, United States

Paul M. Peloso,

• Sainati, Stephen M., Horizon Therapeutics plc, Deerfield, Illinois, United States

Stephen M. Sainati,

• Obermeyer, Katie L., Horizon Therapeutics plc, Deerfield, Illinois, United States

Katie L. Obermeyer,

• Saag, Kenneth G., University of Alabama, Birmingham, Alabama, United States

Kenneth G. Saag,

• Tesser, John, Arizona Arthritis & Rheumatology Associates, P.C., Phoenix, Arizona, United States

John Tesser,

• Majjhoo, Amar Qadir, Clinical Research Institute of Michigan, LLC, St. Clair Shores, Michigan, United States

Amar Qadir Majjhoo,

• Weinblatt, Michael E., Brigham and Women’s Hospital, Boston, Massachusetts, United States

Michael E. Weinblatt,

Background

Twenty four percent of patients with gout¹ and 49% of patients with uncontrolled gout (UCG)² patients have CKD. Pegloticase (a pegylated recombinant uricase which rapidly dissolves urate) is associated with a 42% response rate,³ however preliminary evidence suggests co-therapy with immunomodulation such as methotrexate (MTX) may increase this response.⁴ The ongoing MIRROR randomized controlled trial (RCT) directly compares pegloticase w/wo MTX for UCG. We describe study design and baseline renal characteristics.

Methods

Enrolled patients had a serum urate [SU]≥7 mg/dL, urate lowering therapy failure/intolerance, AND visible tophi, recurrent flare, or chronic gouty arthropathy. Chronic immunosuppression, eGFR<40 ml/min/1.73m², and G6PD deficiency were key exclusion criteria. Patients who tolerated a 2-wk 15 mg/wk oral MTX run-in were randomized 2:1 to receive MTX or placebo (PBO). After a 4-wk MTX or PBO period, patients began 52 wks of pegloticase with weekly MTX or PBO. Primary endpoint is 6-month response rate (% patients with SU<6 mg/dL for ≥80% during Month 6).

Results

42 US sites randomized 152 adults (54.7±12.6 yrs, 89% men, BMI 32.6±6.5 kg/m²) with UCG (SU 8.9±1.6 mg/dL, 13.9±10.7 yr gout history, 68% with clinical tophi). 21% had prior kidney stones. Mean eGFR was 69.7±17.8 ml/min/1.73m² with 32% having eGFR<60 ml/min/1.73m². Gout burden became more severe as CKD stage increased, as indicated by Physician Global Assessment, Health Assessment Questionnaire (HAQ), and affected joint count.

Conclusion

Key baseline renal demographics demonstrate heavy gout disease burden and suggest UCG impacts patients with advanced CKD more severely.

References
1. Roughley MJ et al. Arthritis Res Ther 2015;17:90
2. Francis-Sedlak M et al. Rheumatol Ther 2021;8:183-97
3. Sundy JS et al. JAMA 2011;306:711-20
4. Keenan RT et al. Semin Arthritis Rheum 2021;51:347-52

Mean values of gout severity assessments

Funding

• Commercial Support – Horizon Therapeutics plc