Background/Purpose: Pegloticase is a recombinant DNA-produced porcine-like uricase enzyme which metabolizes relatively insoluble urate to highly soluble allantoin. It is used in the treatment of refractory gout which has failed maximal medical management, typically with xanthine oxidase inhibitors (XOI). Studies have shown a complete responder rate of 42% when defined as repeat serum uric acid levels <6.0mg/dL for >80% of the time during months 3 and 6 of treatment. Therefore 58% of patients failed to maintain repeat serum uric acid levels <6.0mg/dL during this time period. The driving mechanism of this failure has been proposed to be driven by neutralizing antibodies. As is done in treatment of other rheumatologic diseases, coadministration of other medications could potentially temper the development of these neutralizing antibodies. The aim of the current study was to identify and quantify the improvement (as defined by maintenance of response) in patients treated with pegloticase for refractory gouty arthropathy.

Methods: In this prospective, proof-of-concept, case series, 8 patients with refractory tophaceous gouty arthropathy being started on treatment with pegloticase 8mg every 2 weeks were identified. Methotrexate 15mg orally once weekly and folic acid 1mg orally once daily was started one month prior to the initial administration of pegloticase and continued throughout the pegloticase treatment. Serum uric acid was measured every two weeks, prior to each subsequent infusion. At the completion of pegloticase treatment (or end of the observation period, June 1, 2018) the number and percentage of patients able to maintain a serum uric acid at goal <6.0mg/dL was recorded. The primary objective was to evaluate the response rates in patients coadministered methotrexate vs. published response rates (known to be 42%) in those on pegloticase monotherapy between 3 and 6 months of treatment.

Results: Eight patients were identified, from 3 separate infusion centers. Seventy-three total pegloticase infusions were performed within the observation period, with 7 patients receiving at least 8 infusions (4 months) and 3 patients receiving at least 12 infusions (6 months). Of the 8 patients followed, 100% of patients were responders as defined by >80% of serum uric acid levels being maintained at goal <6.0mg/dL during the observation period. Furthermore, there were only 2 patients who each had a single uric acid level above 6.0mg/dL (one following the second infusion and one following the third infusion) and both returned to goal <6.0mg/dL on all subsequent infusions.

Conclusion: Pretreatment and coadministration with methotrexate 15 mg orally once weekly significantly reduced failure rates in pegloticase treated patients with chronic gouty arthropathy. Although additional studies would be needed to corroborate these results, these data support a potential paradigm shift in treatment of refractory gout with pegloticase.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pretreatment-and-coadministration-with-methotrexate-improved-durability-of-pegloticase-krystexxa-response-a-prospective-proof-of-concept-case-series/