Methotrexate added to pegloticase for uncontrolled gout does not negatively affect kidney function, even in the presence of chronic kidney disease (CKD) stage 3, according to study findings presented at the American Society of Nephrology’s Kidney Week 2022 conference in Orlando, Florida.
The findings are from the MIRROR RCT trial, which included patients with uncontrolled gout, defined as serum uric acid levels of 7 mg/dL or higher, failure of or intolerance to urate-lowering therapy, or 1 or more gout symptoms. Previously, the trial showed that pegloticase given with oral methotrexate vs placebo resulted in a higher urate-lowering response rate and a lower infusion reaction rate.
Methotrexate can cause renal toxicity and is contraindicated in advanced CKD.
Following a 2-week methotrexate tolerance test, a team led by Abdul Abdellatif, MD, of Baylor College of Medicine in Houston, Texas, randomly assigned 100 patients to receive pegloticase (biweekly 8 mg infusion) plus oral methotrexate (15 mg/week) and 52 to receive pegloticase plus placebo. A total of 33 patients in the methotrexate arm (33.3%) and 16 patients in the placebo arm (30.8%) had CKD stage 3 (estimated glomerular filtration rate [eGFR] 40-59 mL/min/1.73 m2). The trial excluded patients with an eGFR less than 40 mL/min/1.73 m2.
Randomized patients (intent-to-treat [ITT] population) then entered a 4-week blinded methotrexate/placebo run-in period followed by a 52-week pegloticase plus methotrexate or placebo treatment period. The study’s primary endpoint was urate-lowering response rate during treatment month 6. Investigators examined mean change from baseline in eGFR.
Mean eGFR did not appear to decrease after oral methotrexate initiation. In addition, mean eGFR changes were not significantly different between the methotrexate and placebo arms. Subgroup analyses of patients with an eGFR less than 60 and 60 mL/min/1.73 m2 or higher revealed similar findings.
Disclosure: The study was funded by Horizon Therapeutics, for which Abdul Abdellatif, MD, is a consultant and paid speaker. Other investigators are employees of and stockholders in Horizon.
Abdellatif A, Botson J, Obermeyer K, LaMoreaux B, Marder B. eGFR changes in uncontrolled gout patients randomized to receive methotrexate or placebo as co-therapy to pegloticase: MIRROR RCT findings. Presented at: Kidney Week 2022; November 3-6, Orlando, Florida. Abstract SA-PO898.