Efficacy and Safety of Methotrexate Plus Pegloticase in Uncontrolled Gout

Gloved clinician touching foot
Researchers investigated the safety and efficacy of oral methotrexate as co-therapy with pegloticase for sustained urate-lowering response.

Patients with uncontrolled gout who received combination treatment with pegloticase plus methotrexate (MTX) showed a higher rate of sustained urate-lowering response over 6 months compared with those treated with pegloticase plus placebo, according to study results presented at European Alliance of Associations for Rheumatology (EULAR) Congress 2022, held from June 1 to 5, in Copenhagen, Denmark.

Researchers conducted a randomized, placebo-controlled trial to determine whether treatment with MTX in combination with pegloticase could benefit patients with uncontrolled gout.

Patients with uncontrolled gout were divided into 2 groups: pegloticase plus MTX and pegloticase plus placebo. Uncontrolled gout was defined as (1) serum uric acid (sUA) level of at least 7 mg/dL; (2) oral urate lowering therapy (ULT) failure or intolerance; and (3) at least 1 of the following: (a) 1 or more tophus; (b) 2 or more flares in the prior year; and/or (c) chronic gouty arthritis.

The primary study endpoint was the proportion of month 6 treatment responders (ie, sUA of less than 6 mg/dL for at least 80% of the time during weeks 20 to 24). Exclusion criteria included contraindication to MTX, use of immunosuppressants, glucose-6-phosphate dehydrogenase deficiency, and renal impairment (ie, estimated glomerular filtration rate of less than 40 mL/min/1.73 m2).

The study participants were randomized in a 2:1 ratio to receive either oral MTX (15 mg/week) or placebo. Following a 4-week MTX/placebo run-in, pegloticase was initiated on day 1. Both pegloticase (twice-weekly 8-mg infusions) and MTX/placebo were administered over a 52-week treatment period.

A total of 152 participants (88.8% men) were randomized at 42 sites. Overall, 100 participants received pegloticase plus MTX and 52 participants received pegloticase plus placebo. Four of the MTX participants and 3 of the placebo participants discontinued treatment prior to receiving the initial pegloticase dose. Further, 26 of the participants treated with MTX plus pegloticase patients and 30 of those treated with MTX plus placebo patients discontinued treatment either at or before week 24.

The primary endpoint was met with a 6-month response rate of 71.0% in the pegloticase-plus-MTX group vs 38.5% in the pegloticase-plus-placebo group (P <.0001). During the initial 24 weeks of treatment, 81.3% of participants in the pegloticase-plus-MTX group vs 95.9% of those in the pegloticase-plus-placebo group experienced at least 1 adverse event; gout flare was reported in 66.7% of patients treated with pegloticase plus MTX compared with 69.4% of those treated with pegloticase plus placebo. Infusion reactions were more common among those in the pegloticase-plus-placebo group than in those in the pegloticase-plus-MTX group (30.6% vs 3.1% plus anaphylaxis in 1.0%, respectively).

The study authors concluded that a significantly higher rate of a sustained ULT response over 6 months was observed in patients treated with pegloticase plus MTX compared with those treated with pegloticase plus placebo. No new safety concerns were observed.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Botson J, Saag K, Peterson J, et al. A randomized, double blind placebo controlled, multicenter, study of methotrexate combined with pegloticase in patients with uncontrolled gout. Presented at: EULAR Congress 2022; June 1-4, 2022; Copenhagen, Denmark. Abstract OP0171.