Journal List > J Rheum Dis > v.20(4) > 1064049

Park, Song, Park, Koh, Yoo, Lee, Yoo, Lee, Kim, Choi, Kim, and Jung: The Urate-lowering Efficacy and Safety of Febuxostat in Korean Patients with Gout

Abstract

Objective

To compare the urate-lowering efficacy and the safety of febuxostat, allopurinol and placebo in Korean patients with gout for 4 weeks.

Methods

Subjects (n=182) with gout were randomized to febuxostat (40, 80, 120 mg), allopurinol 300 mg, or placebo group. The primary end point was the proportion of subjects whose serum urate concentration fell to less than 6.0 mg/dL after the 4-week treatment.

Results

The primary end point was reached at 25.7%, 80.0% and 83.3% of patients receiving 40, 80 and 120 mg of febuxostat, respectively, 58.3% of those receiving 300 mg of allopurinol and none of the placebo (p<0.001: each febuxostat dose or allopurinol group versus placebo group, p=0.0484 and p=0.0196: febuxostat 80 and 120 mg compared with allopurinol, respectively). The number and proportion of subjects who developed adverse events (AEs) were 13 subjects (37%), 14 (39%) and 18 (50%) in the febuxostat of 40, 80 and 120 mg group, respectively, 21 (57%) in the allopurinol 300 mg group and 17 (46%) in the placebo group. No statistically significant differences in the incidence rates of adverse events were observed between the groups. There was no significant difference in gout flare-up incidence.

Conclusion

Febuxostat, 80 mg or 120 mg, was more effective than allopurinol (300 mg) or placebo, when lowering the serum urate. The safety of febuxostat and allopurinol was comparable.

References

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Figure 1.
Flow chart of the patient allocation.
jrd-20-223f1.tif
Figure 2.
The proportions of subjects with serum urate levels falling to <6.0 mg/dL after the 4-week treatment. ∗p<0.0001 vs. placebo, Febuxostat 40 mg, 80 mg, 120 mg vs. allopurinol, p=0.0054, 0.0484, 0.0196 respectively. p-value by Fisher's exact test or chi-square test.
jrd-20-223f2.tif
Figure 3.
The frequency of subjects with gout flare-up. There were no significant differences in the incidence of gout flare-up between the groups during the treatment period (p>0.05).
jrd-20-223f3.tif
Table 1.
Baseline characteristics of the gout patients according to the treatment groups
Characteristic Febuxostat 40 mg (n=35) Febuxostat 80 mg (n=36) Febuxostat 120 mg (n=36) Allopurinol 300 mg (n=37) Placebo (n=37) p-value
Age (mean± SD years) 49.6±11.9 48.9±12.3 51.2±9.9 48.6±11.8 51.8±12.4 0.6978
BMI 26.3±3.5 25.1±2.8 25.8±2.1 25.7±3.3 25.7±3.1 0.5421
Alcohol use 20 (57.1) 24 (66.7) 28 (77.8) 26 (70.3) 28 (75.7) 0.3419
Tobacco use 9 (25.7) 13 (36.1) 12 (33.3) 17 (46.0) 14 (37.8) 0.2344
Coexisting conditions           0.9934
  Diabetes mellitus 1 (2.9) 0 (0.0) 0 (0.0) 2 (5.4) 1 (2.7)  
  Dyslipidemia 4 (11.4) 3 (8.3) 5 (13.9) 5 (13.5) 10 (27.0)  
  Hypertension 11 (31.4) 9 (25.0) 8 (22.2) 18 (48.7) 12 (32.4)  
Baseline serum creatinine 1.2±0.1 1.2±0.2 1.2±0.1 1.2±0.1 1.2±0.1 0.3081
Baseline serum urate concentration (mean±SD mg/dL) 9.7±1.1 9.7±1.1 9.5±1.0 9.6±1.0 9.8±1.2 0.8230
 ≥8 mg/dL, <9 mg/dL 9 (25.7) 10 (27.8) 10 (27.8) 10 (27.0) 11 (29.7)  
 ≥9 mg/dL, <10 mg/dL 16 (45.7) 16 (44.4) 16 (44.4) 16 (43.2) 16 (43.2) 1.0000
 ≥10 mg/dL 10 (28.6) 10 (27.8) 10 (27.8) 11 (29.7) 10 (27.0)  
Previous urate-lowering therapy           0.9678
  Allopurinol 18 (51.4) 21 (58.3) 19 (52.7) 21 (56.8) 19 (51.6)  
  Benzbromarone 2 (2.7) 3 (8.3) 3 (8.3) 0 (0.0) 3 (8.1)  

BMI: body mass index.

p-value by ANOVA or Kruscal Wallis test,

p-value by Fisher's exact test or chi-square test,

including hypercholesterolemia and hypertriglyceridemia.

Table 2.
Percent reduction of serum urate concentration from baseline at final visit - ITT population
Treatment group Mean± SD (mg/dL) p-value (vs. placebo) p-value (vs. allopurinol)
Febuxostat 40 mg (N=35) Baseline 9.7±1.1    
  Day 14 6.4±1.0    
  Day 28 6.5±1.2    
  Percent reduction (%) −32.4±12.4 <.0001 0.0116
Febuxostat 80 mg (N=35) Baseline 9.7±1.1    
  Day 14 4.7±0.9    
  Day 28 4.9±1.5    
  Percent reduction (%) −49.0±12.8 <.0001 0.0070
Febuxostat 120 mg (N=36) Baseline 9.5±1.0    
  Day 14 4.3±1.8    
  Day 28 4.2±1.9    
  Percent reduction (%) −55.7±20.4 <.0001 <.0004
Allopurinol 300 mg (N=36) Baseline 9.6±1.0    
  Day 14 5.8±1.3    
  Day 28 5.8±1.5    
  Percent reduction (%) −40.4±13.5 <.0001
Placebo (N=37) Baseline 9.8±1.2    
  Day 14 9.8±1.5    
  Day 28 9.8±1.5    
  Percent reduction (%) 0.9±13.6

p-value by t-test. ITT: intention to treat.

Table 3.
Adverse events occurring >5% of subjects according to each treatment group
  Febuxostat 40 mg (n=35) Febuxostat 80 mg (n=36) Febuxostat 120 mg (n=36) Allopurinol 300 mg (n=37) Placebo (n=37) p-value
Number of subjects with treatment emergent adverse events (TEAEs, %) 13 (37.1) 14 (38.9) 18 (50.0) 21 (56.78) 17 (46.0) NS
  Arthralgia 0 2 (5.6) 2 (5.6) 0 0  
  Diarrhea 2 (5.7) 2 (5.6) 0 1 (2.7) 1 (2.7)  
  Urticaria 0 1 (2.8) 0 0 2 (5.4)  
  Alanine aminotransferase (ALT) increased 7 (20.0) 3 (8.3) 5 (13.9) 4 (10.8) 1 (2.7)  
  Aspartate aminotransferase (AST) increased 4 (11.4) 3 (8.3) 3 (8.3) 4 (10.8) 1 (2.7)  
  Blood bilirubin increased 0 0 0 2 (5.4) 0  
  Hypertriglyceridaemia§ 2 (5.7) 1 (2.8) 1 (2.8) 4 (10.8) 2 (5.4)  
Number of subjects with TEAEs related to drug 7 (20.0) 7 (19.4) 7 (19.4) 13 (35.1) 6 (16.2) NS
Number of subjects with TEAEs leading to withdrawal 0 1 (2.8) 0 2 (5.4) 1 (2.7) NS
Number of subjects with serious TEAEs 0 1 (2.8) 0 1 (2.7) 0 NS
  Coronary artery disease   1 (2.8)        
  Acute pancreatitis       1 (2.7)    
  Renal cell carcinoma stage I       1 (2.7)    

p-value, febuxostat or allopurinol vs. placebo. p-value by chi-square or Fisher's exact test. NS: not significant,

ALT increase above the upper normal limit, 43 IU/L,

AST increase above the upper normal limit, 38 IU/L,

Bilirubin increase above the upper normal limit, 1.2 mg/dL,

§ Triglycerides increase above 200 mg/dL.

Table 4.
Liver function test abnormalities
Febuxostat 40 mg (n=35) Febuxostat 80 mg (n=36) Febuxostat 120 mg (n=36) Allopurinol 300 mg (n=37) Placebo (n=37) p-value
ALT ≥2.0 times the ULN 1 (2.9) 1 (2.8) 1 (2.8) 3 (8.1) 0 NS
AST ≥2.0 times the ULN 0 0 0 1 (2.7) 0 NS

Values are the number of patients (%). ALT: alanine aminotransferase, AST: aspartate aminotransferase, ULN: upper limit of normal.

p-value, febuxostat or allopurinol vs. placebo, NS: not significant.

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