Pretreatment and Coadministration With Methotrexate Improved Durability of Pegloticase Response: An Observational, Proof-of-Concept Case Series

Pegloticase is used for treatment of refractory gout, which has failed maximal medical management, but only 42% of patients respond completely to treatment because of the presumed development of antidrug antibodies, which rapidly clear the pegloticase molecule. Immunomodulatory medications temper antidrug antibody development in other diseases. The aim of this case series was to investigate the utility of adding methotrexate to a pegloticase regimen to increase the response durability in a real-world practice setting. METHODS: In this multicenter, proof-of-concept, observational case series, refractory tophaceous gouty arthropathy patients being started on pegloticase 8 mg every 2 weeks were identified. The patients began oral methotrexate 15 mg/wk and folic acid 1 mg/d, 1 month prior to the initial pegloticase administration, and continued throughout pegloticase treatment. Responders were defined by demonstrating ≥80% of preinfusion serum uric acid (sUA) levels <6.0 mg/dL between months 3 and 6. RESULTS: Ten sequential patients, aged 35 to 80 years, identified between May 2017 and June 2018, from 3 separate infusion centers were followed for up to 10 months. All patients maintained methotrexate 15 mg/wk without dose adjustments. There were 143 total pegloticase infusions. All 10 patients completed a full course of pegloticase treatment with 100% response and no infusion reactions. No patients stopped pegloticase therapy because of increased sUA, loss of response, or gout flares. CONCLUSIONS: Pretreatment and coadministration of methotrexate with pegloticase resulted in 100% maintenance of pegloticase sUA response with no infusion reactions. These data support the potential use of immunomodulation with methotrexate to improve durability of pegloticase response in the treatment of refractory gout.