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. 2021 Apr;51(2):347-352.
doi: 10.1016/j.semarthrit.2021.01.005. Epub 2021 Jan 27.

The effect of immunomodulators on the efficacy and tolerability of pegloticase: a systematic review

Robert T Keenan  1 , John K Botson  2 , Karim R Masri  3 , Lissa Padnick-Silver  4 , Brian LaMoreaux  5 , John A Albert  6 , Michael H Pillinger  7
Affiliations
Free article

The effect of immunomodulators on the efficacy and tolerability of pegloticase: a systematic review

Robert T Keenan et al. Semin Arthritis Rheum. 2021 Apr.
Free article

Abstract

Introduction: Pegloticase is a recombinant PEGylated uricase that converts relatively insoluble urate to highly water-soluble allantoin, which is readily excreted by the kidneys. It is the first and only biologic treatment indicated for refractory or uncontrolled gout. Clinical trials showed a 6-month pegloticase responder rate of 42%, with the non-responder rate largely being attributed to the development of high-titer anti-drug antibodies (ADAs) against pegloticase. Immunomodulation attenuates ADA formation to biologics in a number of autoimmune conditions, but their use with pegloticase for uncontrolled gout is less established. This systematic review examined published cases of refractory gout patients treated with immunomodulation in combination with pegloticase.

Methods: Published cases of immunomodulation with pegloticase were identified in a PubMed search and in abstract databases of major rheumatology society meetings (2012-2020). Duplicate and review articles were excluded, as were those that did not include cases of pegloticase use with immunomodulation. Cases with off-label pegloticase administration schedules were also excluded. Pegloticase response was defined according to each study's specified standard.

Results: Ten publications describing 82 cases of pegloticase use in the setting of immunomodulation were identified. Overall pegloticase response rate was 82.9%. Patients co-treated with an individual immunomodulator had the following response rates: methotrexate: 87.5% (35 of 40 patients), mycophenolate mofetil: 86.4% (19 of 22 patients vs. pegloticase monotherapy [placebo]: 40% [4 of 10 patients]), azathioprine: 63.6% (7 of 11 patients), and leflunomide: 66.7% (4 of 6 patients). A single patient was co-treated with cyclosporin and was a responder. The two patients treated with more than one immunomodulator were both responders.

Conclusion: Published reports suggest that immunomodulation co-therapy has the potential to markedly improve pegloticase responder rates in patients with uncontrolled gout.

Keywords: DMARD; Immunomodulation; Pegloticase; Treatment response.

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Conflict of interest statement

Declarations of Competing Interest RTK has been or is a consultant with Horizon, Selecta Biosciences, Atom Biosciences, Dyve Biosciences, and Sobi; is an advisory board member for Horizon; and has received research support from Sobi and Selecta Biosciences. JKB has received research support from Horizon and Radius Health as a study site and principal investigator and has received consulting/speaker fees from Horizon, Celgene, Novartis, and AbbVie. KRM has received consulting/speaker fees and holds stock in Horizon. LP-S and BL are employees of and hold stock in Horizon. JAA is a consultant with Horizon. MHP has received consulting fees from Horizon and Sobi and investigator-initiated grants from Horizon and Hikma.

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