Changes in eGFR in Patients With Gout During Treatment With Pegloticase

By Victoria Socha - Last Updated: April 11, 2023

Patients with advanced chronic kidney disease (CKD) commonly experience gout, a condition associated with CKD progression. In patients with CKD and uncontrolled gout, pegloticase lowers serum urate. Results of the MIRROR randomized, controlled trial demonstrated a higher response rate with methotrexate (MTX) versus placebo cotherapy (71.09% vs 38.5%). However, according to Abdul Abdellatif, MD, and colleagues, use of MTX had been limited due to the potential risk for an adverse impact on estimated glomerular filtration rate (eGFR) in patients with CKD.

During a poster session at the National Kidney Foundation Spring Clinical Meetings 2023, Dr. Abdellatif et al reported 12-month changes in eGFR among patients in the MIRROR trial. The poster was titled eGFR Changes During Pegloticase Treatment With and Without Methotrexate Cotherapy: 12-Month Findings of MIRROR RCT.

Uncontrolled gout was defined as serum urate ≥7 mg/dL, urate-lowering therapy failure/intolerance, and one or more gout symptoms. Patients with uncontrolled gout were randomized 2:1 to receive oral MTX (15 mg/week) or placebo as cotherapy to pegloticase (8 mg biweekly, 52 weeks). Patients with eGFR <40 mL/min/1.73 m2 were excluded.

Following a 2-week MTX tolerance test and 4-week blinded MTX/placebo run-in period, patients began treatment with pegloticase plus MTX or pegloticase plus placebo. The first dose of pegloticase was Day 1. Measurement of eGFR occurred prior to MTX use, at baseline, and during therapy. Mean change in eGFR from baseline was analyzed by group and by patients with baseline eGFR <60 mL/min/1.73 m2 and patients with baseline eGFR <60 mL/min/1.73 m2 and  ≥60 mL/min/1.73 m2 (intention-to-treat, all randomized patients).

The groups were similar in baseline characteristics: MTX group, n=100; mean age, 56 years; 91% men; baseline eGFR, 68 mL/min/1.73 m2 and placebo group, n=52; mean age, 53 years; 85% men; baseline eGFR, 71 mL/min/1.73 m2. Both groups were stable in eGFR during the run-in and treatment periods.

At week 52, the change in eGFR from baseline in the MTX group was +4.6 mL/min/1.73 m2 versus +1.7mL/min/1.73 m2 in the placebo group. Among patients with baseline eGFR <60 mL/min/1.73 m2, the change from baseline at week 52 was +3.2 mL/min/1.73 m2 in the MTX group and +0.9 mL/min/1.73 m2 in the placebo group.

In conclusion, the researchers said, “eGFR remained stable in most pegloticase-treated patients with or without MTX cotherapy. This also held true for patients with stage 3 CKD at baseline (all eGFR >40). These data suggest renal function was not negatively impacted by treatment with pegloticase plus MTX during the MIRROR RCT.”

Source: Abdellatif A, Botson J, Obermeyer K, Padnick-Silver L, Marder B. eGFR changes during pegloticase treatment with and without methotrexate cotherapy: 12-month findings of MIRROR RCT. Poster #232. Abstract of a poster presented during the National Kidney Foundation Spring Clinical Meetings; April 11-15, 2023; Austin, Texas. Funding for the study was provided by Horizon Therapeutics plc.

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