Expert Opinion on Pegloticase with Concomitant Immunomodulatory Therapy in the Treatment of Uncontrolled Gout to Improve Efficacy, Safety, and Durability of Response

Abstract

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. 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.

Keywords: Antidrug antibodies; Gout; Immunogenicity; Immunomodulation; Pegloticase.

Fig. 1

Proportion of patients receiving pegloticase and concomitant immunomodulatory therapy by year (2015–2019) [•]. ^aPatients who started either methotrexate or azathioprine within 60 days of their first pegloticase infusion