Background 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 (sUA) levels <6.0 mg/dL for >80% of the time during months 3 and 6 of treatment. Patients that do not maintain a low uric acid while on pegloticase therapy are presumed to have developed anti-drug antibodies (ADA) which rapidly clear the pegloticase molecule. As is routinely utilized in the treatment of other rheumatologic diseases, coadministration of immunomodulatory medications, such as methotrexate, could potentially temper the development of these ADAs (as defined by maintenance of sUA response) in patients treated with pegloticase for refractory gouty arthropathy.

Objectives The aim of the current case series was to identify and clinically evaluate patients in a real-world practice setting in order to investigate the utility of adding methotrexate to a pegloticase regimen to increase the durability of response.

Methods In this prospective, proof-of-concept, observational case series, 10 sequential patients with refractory tophaceous gouty arthropathy being started on treatment with pegloticase 8 mg every two weeks (as per the label) were identified from 3 separate infusion centers. No inclusion/exclusion criteria were implemented or prescreening performed. Methotrexate (MTX) 15 mg orally once weekly and folic acid 1 mg orally once daily was started one month prior to the initial administration of pegloticase and continued throughout pegloticase treatment. Any infusion pre-medications, which were consistent with standard practices, were administered per the individual physician’s discretion as well as management of any gout flares which occurred during the treatment course. As per standard of care, sUA was measured every two weeks, prior to each subsequent infusion. At the completion of pegloticase treatment for all patients, the number and percentage of patients able to maintain an sUA at goal <6.0 mg/dL was recorded.

Results Ten patients ranging in age from 35-80 were identified, from 3 separate infusion centers. There were 143 total pegloticase infusions performed within the observation period. All 10 patients received at least 10 infusions (5 months), 9 patients at least 12 infusions (6 months), 5 patients at least 16 infusions (8 months), 2 patients at least 18 infusions (9 months), and 1 patient received 19 infusions. All 10 patients completed a full course of pegloticase treatment. All patients stayed on MTX 15 mg/week. There were no dose adjustments. 100% of patients were responders as defined by >80% of sUA levels being maintained at goal <6.0 mg/dL during the observation period. None of the 10 patients stopped pegloticase therapy due to increased sUA or loss of response and there were no infusion reactions in any of the 143 infusions or safety concerns identified. Gout flares did occur, primarily following the initial infusion, with less severity/prevalence with subsequent infusions. No patients discontinued treatment because of flares.

Conclusion In this proof-of-concept case series of 10 sequential patients, pretreatment and co-administration of methotrexate 15 mg orally once weekly and folic acid 1 mg orally once daily with pegloticase resulted in a 100% maintenance of pegloticase sUA response with no infusion reactions. Although additional studies would be needed to corroborate these results, these data support a potential paradigm shift in treatment of refractory gout with pegloticase.

Reference [1] Sundy JS, et al. JAMA. 2011;306:711

Acknowledgement Research sponsored by the Alaska Rheumatology Alliance.

Disclosure of Interests John Botson Shareholder of: Publicly traded stock: Horizon, Johnson and Johnson, Pfizer, Rigel, Consultant for: Celgene, Eli Lilly, Genentech, Horizon, Mallinckrodt, Novartis, Pfizer, Speakers bureau: Celgene, Eli Lilly, Horizon, Mallinckrodt, Novartis, Pfizer, Jeff Peterson Consultant for: Celgene, Genentech, Horizon, Lilly, Novartis, Regeneron (2017-2018), Speakers bureau: Abbvie, Horizon, Lilly, Novartis (2017-2018)