Curr Rheumatol Rep 2022 Feb 15
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.
Related Questions
At what point, if at all, do you decrease the frequency of or discontinue pegloticase infusions after achieving persistently low serum urate levels?
This is one of the most frequent questions physicians have about pegloticase therapy. To review, the goal of pegloticase therapy is to manage the gout patient who has an overwhelming disease burden from deposits of MSU in joints, bone and soft tissues. Frequent flares, chronic synovitis, tophi inter...
When do you consider discontinuing Pegloticase in a patient with tophaceous gout who has had excellent response to therapy?
This is an important question to clinicians who use pegloticase for their severely afflicted gout patients. There are no studies that provide guidance to answer this question but there is a good rational approach to knowing when to stop treatment.To recap, pegloticase therapy is indicated for patien...
How would you manage a patient on pegloticase and immunomodulation in whom the uric acid has never dropped below 6?
Pegloticase, a PEGylated uricase enzyme infused every two weeks for gout is highly effective but highly immunogenic. Patients responsive to pegloticase typically lower their serum uric acids (SUA) to <0.1mg/dL or thereabout. The initial phase 3 studies had a primary endpoint of sustained uric acid l...