Kidney Function Stable During 12 Months of Pegloticase-Methotrexate for Gout

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Kidney function was not harmed over 52 weeks of pegloticase and methotrexate co-therapy in patients with uncontrolled gout at baseline.

Kidney function remains stable over 12 months in most patients with uncontrolled gout treated with a combination of pegloticase and methotrexate, investigators reported at the National Kidney Foundation’s 2023 Spring Clinical Meetings in Austin, Texas.

Methotrexate is used cautiously in patients with mild to moderate chronic kidney disease (CKD) because it is primarily excreted by the kidneys and can contribute to acute kidney injury. The disease-modifying antirheumatic drug is contraindicated in advanced CKD.

Investigators hypothesized that methotrexate would reduce immunogenicity from treatment with pegloticase, a pegylated mammalian recombinant uricase. Results from the original MIRROR randomized controlled trial (Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Krystexxa) showed a higher urate-lowering response rate (71% vs 39%) and lower infusion reaction risk (4% vs 31%) at 6 months among patients randomly assigned to methotrexate (15 mg/week) or placebo, in combination with pegloticase (8mg biweekly infusion). At baseline, patients had a serum uric acid level of 7mg/dL or higher, failure or intolerance to urate-lowering therapy, and 1 or more gout symptoms. Patients with an estimated glomerular filtration rate (eGFR; in mL/min/1.73 m2) less than 40 using the Modification of Diet in Renal Disease equation were excluded.

At 12 months, urate lowering with pegloticase was sustained in 50.0% and 75.8% of the combination treatment group compared with 25.0% and 43.8% of the placebo recipients who had a baseline eGFR of more than 60 and 40-59, respectively, Abdul Abdellatif, MD, of Baylor College of Medicine in Houston, Texas, and colleagues reported.

Over 12 months, mean eGFR increased by 4.6 in the combination treatment group from a baseline value of 69.8 and increased by 1.7 in the placebo group from a baseline level of 69.7. Among patients in the combination group with a baseline eGFR of more than 60 and 40 to 59, CKD stage improved in 14.0% and 44.4%, remained stable in 72.1% and 48.1%, and worsened in 14.0% and 7.4%, respectively, over 12 months.

Dr Abdellatif’s team concluded that “eGFR remained stable in the majority of uncontrolled gout patients treated with pegloticase both in the presence and absence of [methotrexate] co-therapy.” The investigators noted that they observed this effect in patients with stage 3 CKD and an eGFR higher than 40 at baseline. These study findings extend 6 month results presented at an earlier conference.  

Disclosure: This research was supported by Horizon Therapeutics plc. Please see the original reference for a full list of disclosures.


Abdellatif A, Botson J, Obermeyer K, Padnick-Silver L, Marder B. eGFR changes during pegloticase treatment with and without methotrexate co-therapy: 12-month findings of MIRROR RCT. Presented at: NKF 2023, Austin, Texas, April 11-15. Poster 232.

This article originally appeared on Renal and Urology News