Methotrexate boosts response to pegloticase for gout

Co-treatment with methotrexate (MTX) appears to enhance response rates to pegloticase among patients with uncontrolled gout, according to a study.

The study enrolled adult patients with uncontrolled gout, which was defined as serum urate ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. None of the patients had contraindication to MTX, were currently using immunosuppressant, had G6PDH deficiency, and had estimated glomerular filtration rate <40 ml/minute/1.73 m².

A total of 152 patients were randomized to receive pegloticase (8 mg biweekly) with either oral MTX (15 mg/week; n=100) or placebo (n=52) for 52 weeks.

The primary endpoint of the proportion of treatment responders during month 6 (defined as serum urate <6 mg/dl for ≥80 percent of visits during weeks 20–24) was significantly higher in the MTX group than in the placebo group (71.0 percent vs 38.5 percent, respectively; between-group difference, 32.3 percent, 95 percent confidence interval, 16.3–48.3; p<0.0001).

Over the first 6 months of treatment, 78 of 96 patients (81.3 percent) in the MTX group and 47 of 49 (95.9 percent) in the placebo group experienced ≥1 adverse event (AE). The most common AE was gout flare (66.7 percent and 69.4 percent, respectively).

While the frequency of AEs and serious AEs was comparable between the two groups, the infusion reaction rate was markedly lower in the MTX group (4.2 percent, including one patient who had anaphylaxis) than in the placebo group (30.6 percent; p<0.001). Likewise, there were fewer patients in the MTX group who developed antidrug antibody positivity.