Results of the MIRROR randomized controlled trial comparing cotherapy of pegloticase plus methotrexate (MTX) with pegloticase plus placebo found increased urate-lowering response rate with MTX versus placebo (71.0% vs 38.5% during month 5). Infusion reaction rate was also lower in patients in the pegloticase + MTX group compared with those in the placebo group (4% vs 31%).
Gout is a common comorbidity in patients with chronic kidney disease (CKD). Methotrexate is used cautiously in patients with CKD, making the impact of pegloticase + MTX cotherapy of interest. During a poster session at the American Society of Nephrology Kidney Week 2022, Abdul A. Abdellatif, MD, and colleagues presented changes in estimated glomerular filtration rate (eGFR) among participants in the MIRROR trial. The poster was titled eGFR Changes in Uncontrolled Gout Patients Randomized to Receive Methotrexate or Placebo as Co-Therapy to Pegloticase: MIRROR RCT Findings.
Uncontrolled gout was defined as serum uric acid ≥7 mg/dL, urate-lowering therapy failure/intolerance, and ≥1 gout symptom. Following a 2-week MTX tolerance test and a 4-week blinded MTX/placebo run-in, patients with uncontrolled gout were randomized 2:1 to receive pegloticase (infusion of 8 mg every 2 weeks) and blinded oral MTX (15 mg/week) or placebo (patients with eGFR <40 mL/min/1.73 m2 were excluded).
Baseline eGFR was measured prior to MTX exposure (week 6). Mean change from baseline in eGFR was assessed via treatment and baseline eGFR status (<60 mL/min/1.73 m2 and ≥60 mL/min/1.73 m2). Analyses were performed on all randomized patients (intent-to-treat).
The pegloticase + MTX group included 100 patients. Mean age was 56 years, 91% were male, and mean eGFR was 68.9 mL/min/1.73 m2. The pegloticase + placebo group included 52 patients. Mean age was 53 years, 85% were male, and mean eGFR was 71.1 mL/min/1.73 m2.
In both treatment groups, eGFR was stable during the MTX/placebo run-in and after initiation of pegloticase (day 1). At week 24, mean change in eGFR from baseline was +5.3 mL/min/1.73 m2 in the MTX group (n=70; 69 responders) and +4.3 mL/min/1.73 m2 in the placebo group (n=19; 19 responders). There was no difference in change from baseline in eGFR at week 24 between the eGFR <60 mL/min/1.73 m2 and the ≥60 mL/min/1.73 m2 groups in the MTX cohort (+4.1 mL/min/1.73 m2 and +6.3 mL/min/1.73 m2, respectively) or in the placebo group (+2.5 mL/min/1.73 m2 and +7.8 mL/min/1.73 m2, respectively) (both P≥.48).
In summary, the researchers said, “eGFR did not appear to decrease after oral MTX initiation when administered as cotherapy with pegloticase. This was true for patients with and without pretherapy eGFR <60 mL/min/1.73 m2. These findings suggest MTX cotherapy did not negatively impact renal function in MIRROR RCT trial participants.”
Source: Abdellatif A, Botson JK, Obermeyer KL, LaMoreaux B, Marder BA. eGFR changes in uncontrolled gout patients randomized to receive methotrexate or placebo as co-therapy to pegloticase: MIRROR RCT findings. SA-PO898. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2022; November 5, 2022; Orlando, Florida. Funding for this study was provided by Horizon Therapeutics.