The quality of evidence is downgraded by imprecise results (wide confidence intervals).
A Cochrane review [Abstract] 1 included 5 studies with a total of 1 796 subjects. One study had 3 arms: pegloticase infusion every 2 weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every 2 weeks) and placebo. Two studies looked at lesinurad 200 mg or 400 mg in combination with allopurinol, 1 study examined lesinurad 200 mg or 400 mg in combination with febuxostat, and 1 study compared febuxostat 80 mg and 120 mg to allopurinol.
More participants in the pegloticase every 2 weeks (biweekly) group (table T1) had complete resolution of one or more tophi compared with participants in the placebo group. The results for pegloticase monthly group are shown in table T2. Comparison of the two pegloticase groups found that more participants in the biweekly pegloticase arm had complete resolution of one or more tophi compared with participants in the monthly pegloticase group (RR 1.91, 95% CI 1.03 to 3.55). As pain, function, serum acid normalisation and quality of life data were only presented for the total population in the study, and not for the subgroup with tophi at baseline, these outcomes were not reported in the review. Pegloticase administered biweekly and pegloticase administered monthly resulted in more withdrawals due to adverse events than placebo. Infusion reactions were the most common reason for study discontinuation. Similar number of participants in the pegloticase biweekly group and pegloticase monthly group had an adverse event compared to placebo group. The 3 most common adverse events were gout flares, infusion reactions and headaches; 80% of adverse events were due to flares of gout. Placebo groups did not receive urate lowering therapy, hence were at risk of ongoing gout flares.
| Outcome | Relative effect(95% CI) | NNTB/NNTH (95% CI) | Assumed risk - Placebo | Corresponding risk - Biweekly pegloticase (95% CI) | Participants (studies) |
|---|---|---|---|---|---|
| NA = not applicable | |||||
| Complete resolution of tophi | RR 5.45 (1.38 to 21.54) | NNTB 3 (2 to 6) | 74 per 1000 | 404 per 1000(104 to 1000) | 79 (1 study) |
| Withdrawals due to adverse events | RR 7.59 (1.04 to 55.55) | NNTH 7 (4 to 16) | 23 per 1000 | 177 per 1000(24 to 1000) | 128(1 study) |
| Total adverse events | RR 0.99 (0.91 to 1.07) | NA | 953 per 1000 | 941 per 1000 (851 to 1000) | 128 (1 study) |
| Outcome | Relative effect(95% CI) | NNTB/NNTH (95% CI) | Assumed risk - Placebo | Corresponding risk - Monthly pegloticase (95% CI) | Participants (studies) |
|---|---|---|---|---|---|
| NA = not applicable | |||||
| Complete resolution of tophi | RR 2.86(0.68 to 11.97) | NA | 74 per 1000 | 212 per 1000(52 to 889) | 79(1 study) |
| Withdrawals due to adverse events | RR 8.19(1.12 to 59.71 | NNTH 6 (4 to 14) | 23 per 1000 | 190 per 1000(166 to 1000) | 127 (1 study) |
| Total adverse events | RR 1.05(0.98 to 1.14) | NA | 953 per 1000 | 1000 per 1000(980 to 1000) | 127 (1 study) |
Lesinurad (200 mg or 400 mg) combined with allopurinol was not superior for tophi resolution compared to allopurinol alone (2 studies, n=103). An extension study examined lesinurad 200 mg or 400 mg in combination with febuxostat, or placebo. Participants on lesinurad in the original study continued (CONT) on the same dose. Participants who were not on lesinurad in the original study were randomised (CROSS) to lesinurad 200 mg or 400 mg, both in combination with febuxostat. There were no statistically significant differences in lesinurad 400 mg plus febuxostat (CONT) compared to lesinurad 200 mg plus febuxostat (CONT)(1 study, n=129) nor in lesinurad 400 mg plus febuxostat (CROSS) compared to lesinurad 200 mg plus febuxostat (CROSS)(1 stuy, n=67). It was not possible to determine whether lesinurad plus febuxostat is more effective than placebo. Febuxostat 80 mg or 120 mg was not superior to allopurinol 300 mg for reduction in tophus area or number of tophi (1 study, n=156).
Measurement of serum uric acid level prior to infusion may identify patients who have lost a therapeutic response to pegloticase and may be at increased risk of infusion reactions. Loss of responsiveness to pegloticase is associated with the development of high titer anti-pegloticase antibodies that increase clearance of pegloticase and are associated with a loss of the serum uric acid lowering effect and increased infusion reactions risk.
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