The effect of immunomodulators on the efficacy and tolerability of pegloticase: a systematic review.
Semin Arthritis Rheum
; 51(2): 347-352, 2021 04.
Article
in En
| MEDLINE
| ID: mdl-33601190
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polyethylene Glycols
/
Urate Oxidase
/
Gout Suppressants
/
Gout
/
Immunologic Factors
Type of study:
Clinical_trials
/
Prognostic_studies
/
Systematic_reviews
Limits:
Humans
Language:
En
Journal:
Semin Arthritis Rheum
Year:
2021
Document type:
Article