Introduction: Gout is a painful inflammatory condition caused by chronically elevated serum uric acid levels (sUA). When standard uratelowering therapies fail/are not tolerated, uncontrolled gout (elevated sUA, subcutaneous tophi, chronic gouty arthritis, frequent flares) can occur. Pegloticase, a recombinant uricase, converts uric acid to allantoin, a readily excreted molecule. Responder rate in trials was 42%, limited by anti-drug antibody (ADA) development. Immunomodulators attenuate ADA formation and case reports suggest immunomodulation increases pegloticase responder rates. The current study retrospectively examined responder rate in patients undergoing methotrexate/pegloticase co-therapy. Methods: Patients who underwent methotrexate/pegloticase co-treatment at a single rheumatology practice were included. Demographics, clinical, treatment, and safety Digital Features To view digital features for this article go to

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Purpose of Review Gout is a systemic disease from which some patients develop numerous painful tophi that adversely affect quality of life and functionality. Some patients treated with oral urate-lowering therapy are unable to maintain serum urate levels below 6 mg/dL, and these patients, thus classified as having refractory or uncontrolled gout, often require therapy with pegloticase to reduce symptoms and tophaceous burden. The objective of this expert opinion review is to summarize the available evidence supporting the use of concomitant immunomodulators with pegloticase to prevent development of anti-drug antibodies (ADAs) when treating patients with uncontrolled gout. Recent Findings Emerging evidence suggests that adding an immunomodulator to pegloticase therapy can substantially increase response rates to double those observed in phase 3 randomized controlled trials. Summary The combination of immunomodulation with pegloticase should be considered in routine clinical practice to improve durability of response, efficacy, and safety among patients with uncontrolled gout who otherwise have limited therapeutic options.

Objective: Patients with uncontrolled/refractory gout have heavy disease burden, but few treatment options. Pegloticase lowers serum urate (SU), but anti-drug antibodies can limit treatment efficacy. Evidence supports immunomodulator-pegloticase co-administration to increase sustained urate-lowering rates, but published cases are limited. This study investigated experience with pegloticase-immunomodulation co-therapy at two community rheumatology practices. Methods: Patients initiating pegloticase with immunomodulation in 2017 or later were included. Patient/treatment characteristics and proportion of responders (C 12 pegloticase infusions, SU \ 6 mg/dl at infusion-12) were examined. Patients on therapy at data collection with \ 12 infusions were excluded from response analyses. eGFR before and after therapy was examined.

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