Tolerance of methotrexate co-administered with pegloticase in patients with uncontrolled gout: overview of the findings from the mirror RCT.

BACKGROUND: The efficacy of pegloticase in uncontrolled gout can be limited by antidrug antibody (ADA) formation. Methotrexate (MTX) reduces ADA development, but carries risks, including hepatotoxicity, myelosuppression, and gastrointestinal toxicity. This post hoc analysis of MIRROR evaluated MTX safety in patients with uncontrolled gout receiving pegloticase. RESEARCH DESIGN AND METHODS: Patients with uncontrolled gout were randomized 2:1 to receive pegloticase (8-mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or placebo (PBO) for 52 weeks. Safety data were collected from patients receiving ≥ 1 dose of blinded MTX or PBO during the run-in period and patients receiving ≥ 1 pegloticase infusion during treatment. RESULTS: In the safety population (n = 96 for MTX and n = 49 for PBO), treatment-emergent adverse events were similar between groups. Liver enzymes and Fibrosis-4 Index scores, a predictor of hepatic fibrosis progression, were similar at Week 52. Stomatitis was rare (n = 1). Renal function remained stable in both groups. Liver function did not worsen among alcohol users and chronic kidney disease subgroups. CONCLUSIONS: MTX co-administration with pegloticase did not increase the incidence of liver dysfunction or infection in a post hoc analysis of MIRROR, suggesting that MTX was well tolerated in patients with uncontrolled gout. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ identifier is NCT03994731.