Two review authors extracted data from titles, abstracts and selected studies for detailed review, and extracted data and risk of bias independently. Major outcomes were number of participants with complete resolution of tophi, number of study participant withdrawals due to adverse events,
joint pain reduction, function, quality of life, serum
urate normalisation and total adverse events.
MAIN RESULTS: Only one study, at low risk of all biases, met the inclusion criteria. This was the pooled results from two RCTs (225 participants, 145 with tophi at baseline) randomised to one of three arms;
pegloticase infusion every two weeks (biweekly), monthly
pegloticase infusion (
pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Moderate-quality evidence from one study indicated that biweekly
pegloticase 8 mg infusion reduced tophi in the subset of participants with tophi, but increased withdrawals due to adverse events in all participants, and monthly infusion appeared to result in less benefit.Biweekly
pegloticase treatment resulted in resolution of tophi in 21/52 participants compared with 2/27 who received placebo (risk ratio (RR) 5.45, 95% confidence intervals (CI) 1.38 to 21.54; number needed to treat for an additional beneficial outcome (NNTB) 3 (95% CI 2 to 6).Eleven of 52 participants with monthly
pegloticase treatment had complete resolution of one or more tophi compared with 2/27 who received placebo (RR 2.86, 95% CI 0.68 to 11.97).Participant-reported
pain relief of 30% or greater, function, quality of life, serum
urate normalisation, were reported for all participants but not separately for those with tophi; therefore, we did not include the results.Pegloticase administered biweekly resulted in more withdrawals due to adverse events compared with placebo (15/85 participants with
pegloticase versus 1/43 participants with placebo; RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for an additional harmful outcome (NNTH) 7, 95%
CI 4 to 17).
Pegloticase administered monthly also resulted in more withdrawals due to adverse events than placebo (16/84 participants with
pegloticase versus 1/43 participants with placebo; RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95%
CI 4 to 14). Most withdrawals were due to infusion reactions.Total adverse events were high in all treatment groups: 80/85 participants administered
pegloticase biweekly reported an adverse event compared with 41/43 from the placebo group (RR 0.99, 95% CI 0.91 to 1.07); 84/84 participants administered
pegloticase monthly reported an adverse event versus 41/43 in the placebo group (RR 1.05, 95% CI 0.98 to 1.14). As 80% of adverse events were due to flares of
gout, probably unrelated to the
drug treatment per se, this may explain the high rate of adverse events in the placebo group - who were essentially untreated.
AUTHORS' CONCLUSIONS: