Background/Purpose: Pegloticase is an infused biologic for uncontrolled gout patients that is highly effective but can cause anti-drug antibodies that lead to a lack of therapeutic response. Based on data from randomized clinical trials, 42% of uncontrolled gout patients treated with pegloticase remain responders at 6 months of therapy. Low to moderate levels of immunomodulation treatment with medications such as methotrexate have been shown to attenuate the formation of anti-drug antibodies to biologic medicines in patients with rheumatoid arthritis. There are published cases in gout patients suggesting that low to moderate doses of methotrexate or azathioprine attenuate the development of anti-drug antibodies to pegloticase, allowing uncontrolled gout patients in need of pegloticase therapy to remain on the medicine and achieve a more complete therapeutic outcome. The objective of the present case series was to determine whether exposure to oral or subcutaneous (subQ) methotrexate improved gout patients’ response to pegloticase in a single community rheumatology practice.

Methods: A retrospective chart review was conducted in a rheumatology practice where uncontrolled gout patients starting pegloticase therapy are typically co-treated with methotrexate. All patients receiving any form or schedule of methotrexate before or while on pegloticase were included, and data extracted on their response including duration of pegloticase therapy, gout flares, infusion reactions, methotrexate dosing details, and lab values including uric acid levels, liver function tests, renal function, hemoglobin and white blood cell count. Complete blood count (CBC) and comprehensive metabolic panel (CMP) parameters were monitored closely in all patients treated with methotrexate.

Results: Ten uncontrolled gout patients fit the inclusion criteria. Nine patients were male, the average age was 52.3 years, and all had visible tophi. Methotrexate exposure varied, with 1 patient receiving oral and 9 receiving subQ administration; all but 1 patient started on methotrexate prior to pegloticase, and most patients received 25 mg of methotrexate subQ weekly. Of the 10 patients, at the time of data cutoff, 5 were complete responders, having received an average of 16.4 doses or ~32 weeks of therapy. Three were responding and still actively on pegloticase at the time of data extraction, having received 10, 5 and 2 doses respectively. Two patients had ceased therapy, 1 for loss of response and a mild infusion reaction and 1 due to methotrexate injection related issues. One patient had a gout flare requiring prednisone treatment. LFTs and CBC parameters remained stable during therapy with both methotrexate and pegloticase except for 1 patient who had a mild, transient alcohol-related LFT elevation and pancytopenia that improved with transfusion and cessation of methotrexate. This patient remained on pegloticase and continued as a responder.

Conclusion: When used concurrently with pegloticase, methotrexate appears to attenuate the formation of clinically significant anti-drug antibodies allowing uncontrolled gout patients to receive a more complete duration of pegloticase therapy. No new safety concerns were noted during this project.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/subcutaneous-or-oral-methotrexate-exposure-and-response-to-pegloticase-in-uncontrolled-gout-patients-in-a-community-rheumatology-practice/