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. 2022 Jul 25;18(9):543–549. doi: 10.1038/s41584-022-00804-5

Table 2.

Flare outcomes during pivotal clinical trials of urate-lowering therapy for gout

Trials Flare outcomes in the early trial period Flare outcomes in the late trial period Flare outcomes for the entire trial period Ref.
FACT (Becker et al. 2005) Day 1 to week 8: more participants with gout flare in the febuxostat 120 mg group than in the allopurinol group (36% vs 21%; P< 0.001)

Weeks 9–52: no difference in the proportion of participants with gout flare in the febuxostat 120 mg group compared with the allopurinol group (70% vs 64%)

Weeks 49–52: no difference in the proportion of participants with gout flare in the febuxostat 120 mg group compared with the allopurinol group (6% vs 11%)

Not reported 24
C0405 and C0406 (Sundy et al. 2011)

Months 1–3: higher gout flare incidence in the bi-weekly pegloticase group than in the placebo group (75% vs 53%; P = 0.02)

Months 1–3: more gout flares in the bi-weekly pegloticase group than in the placebo group (mean 2.3 vs 1.2; P = 0.001)

Months 4–6: lower gout flare incidence in the bi-weekly pegloticase group than in the placebo group (41% vs 67%; P = 0.007)

Months 4–6: fewer gout flares in the bi-weekly pegloticase group than in the placebo (mean 0.8 vs 1.3; P = 0.06)

Not reported 26
CLEAR-1 (Saag et al. 2017) Not reported Months 7–12: no difference in the lesinurad 400 mg group and the placebo group (mean 0.51 vs 0.58; P = 0.61) Not reported 33
Doherty et al. 2018 Year 1: more participants in the nurse-led group than in the usual care group experienced ≥2 gout flares (54% vs 40%, risk ratio 1.36 (95% CI 1.05–1.77)) Year 2: fewer participants in the nurse-led group than in the usual care group experienced ≥2 gout flares (8% vs 24%, risk ratio 0.33 (95% CI 0.19–0.57)) Not reported 25
CSP594 (O’Dell et al. 2022)

Weeks 0–48: proportion of participants experiencing one or more gout flares not reported

Secondary end point: weeks 0–24: no difference in gout flare rate in the allopurinol group and the febuxostat group (2.09 vs 2.25 flares per person years; rate ratio 0.93 (95% CI 0.81–1.06))

Secondary end point: weeks 25–48: no difference in gout flare rate in the allopurinol group and the febuxostat group (1.60 vs 1.59 flares per person years; rate ratio 1.00 (95% CI 0.85–1.18))

Primary end point: weeks 49–72: fewer participants with gout flares in the allopurinol group than in the febuxostat group (36.5% vs 43.5%; risk ratio −7 (95% CI −∞ to −1.2); P < 0.001 for non-inferiority of allopurinol)

Secondary end point: weeks 49–72: fewer gout flares in the allopurinol group than in the febuxostat group (1.48 vs 2.02 flares per person years; rate ratio 0.73 (95% CI 0.63–0.86))

Proportion of participants experiencing one or more gout flares over the entire study period not reported

Gout flare rate over the entire study period reported in the manuscript: fewer gout flares in the allopurinol group than in the febuxostat group (1.73 vs 1.97 flares per person-years, rate ratio 0.88 (95% CI 0.81–0.96))

27

Trials in this table represent the major phase III trials for urate-lowering therapy approved by the FDA since 2009 or large investigator-initiated strategy trials (>500 participants). Where more than one dose was tested, data for the highest dose are presented.