Abstract 758: Gout Flare Incidence in Relation to Average Serum Urate during the First Year of Urate-Lowering Therapy
Assil Saleh
Authors:
M. A. Becker, P. A. MacDonald, B. J. Hunt, C. Lademacher, N. Joseph-Ridge.
Background:
Reducing serum levels of urate to <6.0 mg/dL has been shown to reduce the incidence of gout flares in patients. This prospective study analyzed the relationship between serum urate levels and gout flare incidence among a large group of gout patients who underwent urate reducing therapy for up to one year.
Methods:
1832 patients with a history of gout and a baseline serum urate ≥8.0 mg/dL were randomized to receive daily placebo, allopurinol (300mg, or 100mg in case of renal insufficiency), or febuxostat (80mg, 120mg, or 240mg) therapy. This cohort’s subjects were participants of the APEX trial (a 28-week) or the FACT trial (a 52-week), both were double blind clinical trials set out to assess the safety and efficacy of febuxostat in the treatment of gout. Serum urate levels and the incidence of acute gouty flares which necessitated treatment were tracked in all subjects. During the first two months of the trials, all subjects received gout flare prophylaxis with colchicine or naproxen.
Results:
During weeks 9 to 12 of therapy, flare incidence tended to be significantly lower in those with lower average post baseline serum urate levels. During weeks 25 to 28 of therapy, the rates of gout flares were not significantly related to average post baseline serum urate levels.
During weeks 49 to 52 of therapy, incidence of gouty flares was significantly lower in subjects with baseline serum urate levels <6.0 mg/dL than those whose baseline urate levels were >6.0 mg/dL.
Average post baseline sUA |
% of subjects with at least one flare during |
||
Weeks 9 to 12* |
Weeks 25 to 28 |
Weeks 49 to 52* |
|
< 4.0 mg/dL |
42% (141/335) |
12% (36/291) |
4% (4/89) |
4.0 to < 5.0 mg/dL |
38% (130/343) |
15% (43/287) |
5% (7/132) |
5.0 to < 6.0 mg/dL |
34% (116/344) |
13% (38/296) |
7% (9/125) |
6.0 to < 7.0 mg/dL |
33% (83/249) |
18% (39/217) |
11% (10/94) |
7.0 to < 8.0 mg/dL |
28% (37/133) |
15% (17/117) |
16% (7/43) |
≥ 8.0 mg/dL |
28% (56/197) |
17% (26/154) |
18% (4/22) |
*Statistically significant relationship with sUA using Cochran-Armitage trend test |
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Conclusions:
The authors concluded that during early urate-reducing therapy for gout, lower baseline serum urate levels are associated with increased flare risk in patients who are not undergoing prophylaxis. Continued urate-reducing therapy reverses this pattern, and at one year, significantly lower flare rates are observed in subjects whose average post baseline serum urate levels were <6.0 mg/dL.
Editorial Comments:
This is a well designed, large study that illustrates the complexity of the relationship between post baseline serum urate levels and the risk for gout flare. The current study suggests that sustaining low serum urate levels (<6.0 mg/dl) is as crucial as decreasing serum urate early in the treatment course in preventing gouty flares long term (up to one year in this study). The appropriate duration of prophylaxis with colchicine or non-steroidal Anti-inflammatory Drugs remains to be answered. Participants in this study were on prophylaxis for a relatively brief eight weeks. In contrast, prophylaxis for up to 12 months has been reported in other studies. This may have implications for the relevance of these results in clinical practice.
