medwireNews: The addition of methotrexate to pegloticase for the treatment of uncontrolled gout improves the rate of sustained urate-lowering response over 6 months, show findings from the MIRROR randomized controlled trial.
Pegloticase significantly lowers serum uric acid in patients with refractory gout, with levels “often becoming undetectable,” said John Botson (Orthopedic Physicians Alaska, Anchorage, USA) at the EULAR 2022 Congress in Copenhagen, Denmark.
But he added that “the medication is limited because of its ability to create anti-drug antibodies; about 50% of the patients or less will actually respond to completion.”
As methotrexate prevents the development of these anti-drug antibodies, combining it with pegloticase provided the rationale for the study.
Botson and team randomly assigned 152 patients with gout refractory to oral urate-lowering therapy (average serum uric acid levels of 9 mg/dL) to receive weekly methotrexate 15 mg or placebo for a 4-week run-in period followed by the initiation of pegloticase, administered as 8 mg infusions every 2 weeks for 52 weeks.
The response rate at 6 months, defined as a serum uric acid level below 6 mg/dL for at least 80% of the time during the last 5 weeks of the study, was 71% among the 100 patients receiving pegloticase plus methotrexate, which was significantly higher than the 38.5% rate seen among the 52 patients given pegloticase plus placebo.
A treatment benefit with add-on methotrexate was also seen for secondary endpoints, including a significant 2.43 mg/dL greater decline in mean serum uric acid levels from baseline over the 6-month period, with a significant difference evident at all timepoints, and a greater proportion of patients with complete resolution of at least one tophus, at 34.6% with add-on methotrexate versus 13.8% without.
The safety profile was similar for the two treatment arms, with at least one treatment-emergent adverse event in the first 24 weeks occurring in 81.3% of patients taking pegloticase plus methotrexate and 95.9% of those given placebo, but these were mild in at least 95% of patients in either group. And Botson noted that that there were fewer infusion reactions with the addition of methotrexate to pegloticase, at 4.2% versus 30.6% with pegloticase plus placebo.
The rate of serious adverse events was comparable for the two treatment groups, although there were two deaths in the pegloticase plus methotrexate treatment group: one unrelated cardiac arrest and one COVID-19 infection.
The rate of gout flare decreased over time in both treatment arms and there was no significant difference between the two groups.
“This trial confirms not only improved efficacy, but improved safety in patients treated with pegloticase in combination with methotrexate 15 mg orally once weekly,” Botson concluded.
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