Background: Pegloticase is an infused biologic approved to treat uncontrolled gout. The drug is highly effective, but patients can develop anti-drug antibodies that interfere with efficacy.1 Randomized clinical trials have shown that 42% of patients treated with bi-weekly pegloticase had a serum uric acid (sUA) below 6.0 mg/dl at 3 and 6 months.2 Mild-to-moderate immunomodulation has been shown to lower the prevalence of anti-drug antibody formation in patients with other autoimmune diseases (rheumatoid arthritis, Crohn’s disease, juvenile idiopathic arthritis).3 Cases published in the literature suggest that low-to-moderate doses of methotrexate4,5 or azathioprine6 may also attenuate anti-pegloticase antibody formation in uncontrolled gout patients. Therefore, immunomodulation may allow patients to remain on pegloticase therapy longer and achieve a more complete therapeutic response.
Objectives: To examine pegloticase treatment response in patients co-treated with methotrexate.
Methods: This retrospective chart review included patients from a single community rheumatology practice who began pegloticase (8 mg every 2 weeks) therapy between January 2017 and September 2019 and were co-treated with methotrexate. Unless contraindicated, methotrexate co-treatment with pegloticase is now standard in this practice and all patients undergo close monitoring of laboratory parameters including serum uric acid level (sUA), blood counts, and liver function tests (LFTs). To maximize the number of cases, patients administered methotrexate in any form were included. Collected data included demographic information, laboratory values, methotrexate treatment parameters (timing with respect to pegloticase therapy, dose, route), pegloticase response parameters (number of infusions, duration of therapy), and adverse events. Main outcome measures included the number of pegloticase infusions administered (responder defined as ≥12 infusions administered) and therapy duration.
Results: Ten patients (9 male) were included. All patients had visible tophi and average patient age was 52.3 ± 13.5 years. Nine patients began subcutaneous methotrexate (25 mg weekly) an average of 19.9 ± 7.0 days (range: 14 to 35 days) before the first pegloticase infusion. The remaining patient began oral methotrexate (12.5 mg weekly) 14 days after the first pegloticase infusion. Eight of 10 patients (80%) were considered responders, receiving an average of 15.5 ± 3.8 pegloticase infusions (range: 12-21 infusions) over 31.8 ± 9.5 weeks (range: 22.1 to 48.3 weeks). In these 8 responders, mean sUA was 0.2 ± 0.0 mg/dL immediately prior to the last pegloticase infusion. All 10 patients had an initial, rapid decrease in sUA, but two patients discontinued treatment before infusion 12. One patient had increased sUA with a mild infusion reaction, and one patient was lost to follow-up after infusion 5. No new safety concerns emerged. A gout flare occurred in 1 patient and was treated with prednisone. LFT and blood cell parameters were stable over the study period, except in two patients. One had a mild, transient LFT elevation that resolved without treatment, one had an LFT elevation and pancytopenia that improved with methotrexate discontinuation and transfusion, respectively. This patient remained on pegloticase and continued as a responder.
Conclusion: This case series suggests that methotrexate, when used as a co-therapy with pegloticase, allows more patients to complete therapy and to achieve the full therapeutic response. No new safety concerns emerged.
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Disclosure of Interests: : John Albert Consultant of: Horizon Therapeutics, Speakers bureau: Horizon Therapeutics, Tony Hosey Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics
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