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Review
. 2012 Nov 14;11(11):CD008653.
doi: 10.1002/14651858.CD008653.pub2.

Febuxostat for treating chronic gout

Jean H Tayar  1 , Maria Angeles Lopez-Olivo, Maria E Suarez-Almazor
Affiliations
Review

Febuxostat for treating chronic gout

Jean H Tayar et al. Cochrane Database Syst Rev. .

Abstract

Background: Gout is the most common inflammatory arthritis in men over 40 years and has an increasing prevalence among postmenopausal women. Lowering serum uric acid levels remains one of the primary goals in the treatment of chronic gout. In clinical trials, febuxostat has been shown to be effective in lowering serum uric acid levels to < 6.0 mg/dL.

Objectives: To evaluate the benefits and harms of febuxostat for chronic gout.

Search methods: We searched The Cochrane Library, MEDLINE, EMBASE, and International Pharmaceutical Abstracts from inception to July 2011. The ClinicalTrials.gov website was searched for references to trials of febuxostat. Our search did not include any restrictions.

Selection criteria: Two authors independently reviewed the search results and disagreements were resolved by discussion. We included any controlled clinical trial or open label trial (OLT) using febuxostat at any dose.

Data collection and analysis: Data and risk of bias were independently extracted by two authors and summarised in a meta-analysis. Continuous data were expressed as mean difference and dichotomous data as risk ratio (RR).

Main results: Four randomised trials and two OLTs with 3978 patients were included. Risk of bias differed by outcome, ranging from low to high risk of bias. Included studies failed to report on five to six of the nine outcome measures recommended by OMERACT. Patients taking febuxostat 120 mg and 240 mg reported more frequent gout flares than in the placebo group at 4 to 28 weeks (RR 1.7; 95% CI 1.3 to 2.3, and RR 2.6; 95% CI 1.8 to 3.7 respectively). No statistically significant differences were observed at 40 mg and 80 mg. Compared to placebo, patients on febuxostat 40 mg were 40.1 times more likely to achieve serum uric acid levels < 6.0 mg/dL at 4 weeks (95% CI 2.5 to 639), with an absolute treatment benefit of 56% (95% CI 37% to 71%). For febuxostat 80 mg and 120 mg, patients were 68.9 and 80.7 times more likely to achieve serum uric acid levels < 6.0 mg/dL at their final visit compared to placebo (95% CI 13.8 to 343.9, 95% CI 16.0 to 405.5), respectively; with an absolute treatment benefit of 75% and 87% (95% CI 68 to 80% and 81 to 91%), respectively. Total discontinuation rates were significantly higher in the febuxostat 80 mg group compared to placebo (RR 1.4; 95% CI 1.0 to 2.0, absolute risk increase 11%; 95% CI 3 to 19%). No other differences were observed.When comparing allopurinol to febuxostat at 24 to 52 weeks, the number of gout flares was not significantly different between the two groups, except for febuxostat 240 mg (RR 2.3; 95% CI 1.7 to 3.0). Patients on febuxostat 40 mg showed no statistically significant differences in benefits or harms. Patients on febuxostat 80 mg and 120 mg were 1.8 and 2.2 times more likely to achieve serum uric acid levels < 6.0 mg/dL at their final visit (95% CI 1.6 to 2.2, 95% CI 1.9 to 2.5) with an absolute treatment benefit of 29% and 44% (95% CI 25% to 33%, 95% CI 38% to 50%), respectively, at 24 to 52 weeks. Total discontinuation rates were higher for febuxostat 80 mg and 120 mg compared to allopurinol (RR 1.5; 95% CI 1.2 to 1.8, absolute risk increase 11%; 95% CI 6% to 16%; and RR 2.6; 95% CI 2.0 to 3.3, absolute risk increase 20%; 95% CI 3% to 14%, respectively). Discontinuations due to adverse events were similar across groups. Total adverse events were lower for febuxostat 80 mg and 120 mg compared with allopurinol (RR 0.93; 95% CI 0.87 to 0.99, absolute risk increase 6%; 95% CI 0.7% to 11%; and RR 0.90; 95% CI 0.84 to 0.96, absolute risk increase 8%; 95% CI 3% to 13%, respectively). No other relevant differences were noted.After 3 years of follow-up there were no statistically significant differences regarding effectiveness and harms between febuxostat 80 mg or 120 mg and allopurinol groups (adverse event rate per 100 patient-years 227, 216, and 246, respectively).

Authors' conclusions: Although the incidence of gout flares requiring treatment may be increased in patients taking febuxostat compared to placebo or allopurinol during early treatment, no such increase in gout flares was observed in the long-term follow-up study when compared to allopurinol. Febuxostat at any dose was shown to be beneficial in achieving serum uric acid levels < 6.0 mg/dL and reducing serum uric acid levels in the period from baseline to final visit when compared to placebo and to allopurinol. However, the grade of evidence ranged from low to high, which indicates that further research is needed.

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Conflict of interest statement

None known. This systematic review did not receive specific funding.

Figures

1
1
Diagram of study selection. * RCT plus abstract (2 publications)
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
People not affected by a treatment (green faces for those with a good outcome and red for those with a bad outcome) 
 People for which treatment changes their category from a bad outcome to a good outcome (yellow faces) 
 People for which treatment causes an adverse event and changes their category from a good outcome to bad outcome (crossed out green faces)
5
5
People not affected by a treatment (green faces for those with a good outcome and red for those with a bad outcome) 
 People for which treatment changes their category from a bad outcome to a good outcome (yellow faces) 
 People for which treatment causes an adverse event and changes their category from a good outcome to bad outcome (crossed out green faces)
1.1
1.1. Analysis
Comparison 1 Efficacy ‐ febuxostat 40 mg/day versus placebo, Outcome 1 Incidence of gout flares.
1.2
1.2. Analysis
Comparison 1 Efficacy ‐ febuxostat 40 mg/day versus placebo, Outcome 2 Serum uric acid <6.0 mg/dL at final visit.
1.3
1.3. Analysis
Comparison 1 Efficacy ‐ febuxostat 40 mg/day versus placebo, Outcome 3 Change in serum uric acid concentration from baseline at final visit.
2.1
2.1. Analysis
Comparison 2 Efficacy ‐ febuxostat 80 mg/day versus placebo, Outcome 1 Incidence of gout flares.
2.2
2.2. Analysis
Comparison 2 Efficacy ‐ febuxostat 80 mg/day versus placebo, Outcome 2 Serum uric acid <6.0 mg/dL at final visit.
2.3
2.3. Analysis
Comparison 2 Efficacy ‐ febuxostat 80 mg/day versus placebo, Outcome 3 Change in serum uric acid concentration from baseline at final visit.
3.1
3.1. Analysis
Comparison 3 Efficacy ‐ febuxostat 120 mg/day versus placebo, Outcome 1 Incidence of gout flares.
3.2
3.2. Analysis
Comparison 3 Efficacy ‐ febuxostat 120 mg/day versus placebo, Outcome 2 Serum uric acid <6.0 mg/dL at final visit.
3.3
3.3. Analysis
Comparison 3 Efficacy ‐ febuxostat 120 mg/day versus placebo, Outcome 3 Change in serum uric acid concentration from baseline at final visit.
4.1
4.1. Analysis
Comparison 4 Efficacy ‐ febuxostat 240 mg/day versus placebo, Outcome 1 Incidence of gout flares.
4.2
4.2. Analysis
Comparison 4 Efficacy ‐ febuxostat 240 mg/day versus placebo, Outcome 2 Serum urate <6.0 mg/dl at final visit.
4.3
4.3. Analysis
Comparison 4 Efficacy ‐ febuxostat 240 mg/day versus placebo, Outcome 3 Change in serum urate concentration from baseline at final visit.
5.1
5.1. Analysis
Comparison 5 Efficacy ‐ Febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 1 Incidence of gout flares.
5.2
5.2. Analysis
Comparison 5 Efficacy ‐ Febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 2 Serum urate <6.0 mg/dL at final visit.
6.1
6.1. Analysis
Comparison 6 Efficacy ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 1 Incidence of gout flares.
6.2
6.2. Analysis
Comparison 6 Efficacy ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 2 Serum uric acid <6.0 mg/dL at final visit.
6.3
6.3. Analysis
Comparison 6 Efficacy ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 3 Change in serum uric acid concentration from baseline at final visit.
7.1
7.1. Analysis
Comparison 7 Efficacy ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 1 Incidence of gout flares.
7.2
7.2. Analysis
Comparison 7 Efficacy ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 2 Serum uric acid <6.0 mg/dL at final visit.
7.3
7.3. Analysis
Comparison 7 Efficacy ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 3 Change in serum uric acid concentration from baseline at final visit.
8.1
8.1. Analysis
Comparison 8 Efficacy ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 1 Incidence of gout flares.
8.2
8.2. Analysis
Comparison 8 Efficacy ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 2 Serum uric acid <6.0 mg/dL at final visit.
8.3
8.3. Analysis
Comparison 8 Efficacy ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 3 Change in serum uric acid concentration from baseline at final visit.
9.1
9.1. Analysis
Comparison 9 Withdrawals ‐ febuxostat 40 mg/day versus placebo, Outcome 1 TOTAL.
9.2
9.2. Analysis
Comparison 9 Withdrawals ‐ febuxostat 40 mg/day versus placebo, Outcome 2 Adverse event.
9.3
9.3. Analysis
Comparison 9 Withdrawals ‐ febuxostat 40 mg/day versus placebo, Outcome 3 Gout flare.
9.4
9.4. Analysis
Comparison 9 Withdrawals ‐ febuxostat 40 mg/day versus placebo, Outcome 4 Lack of efficacy.
9.5
9.5. Analysis
Comparison 9 Withdrawals ‐ febuxostat 40 mg/day versus placebo, Outcome 5 Other reasons.
10.1
10.1. Analysis
Comparison 10 Withdrawals ‐ febuxostat 80 mg/day versus placebo, Outcome 1 TOTAL.
10.2
10.2. Analysis
Comparison 10 Withdrawals ‐ febuxostat 80 mg/day versus placebo, Outcome 2 Adverse event.
10.3
10.3. Analysis
Comparison 10 Withdrawals ‐ febuxostat 80 mg/day versus placebo, Outcome 3 Gout flare.
10.4
10.4. Analysis
Comparison 10 Withdrawals ‐ febuxostat 80 mg/day versus placebo, Outcome 4 Lack of efficacy.
10.5
10.5. Analysis
Comparison 10 Withdrawals ‐ febuxostat 80 mg/day versus placebo, Outcome 5 Other reasons.
11.1
11.1. Analysis
Comparison 11 Withdrawals ‐ febuxostat 120 mg/day versus placebo, Outcome 1 TOTAL.
11.2
11.2. Analysis
Comparison 11 Withdrawals ‐ febuxostat 120 mg/day versus placebo, Outcome 2 Adverse event.
11.3
11.3. Analysis
Comparison 11 Withdrawals ‐ febuxostat 120 mg/day versus placebo, Outcome 3 Gout flare.
11.4
11.4. Analysis
Comparison 11 Withdrawals ‐ febuxostat 120 mg/day versus placebo, Outcome 4 Lack of efficacy.
11.5
11.5. Analysis
Comparison 11 Withdrawals ‐ febuxostat 120 mg/day versus placebo, Outcome 5 Other reasons.
12.1
12.1. Analysis
Comparison 12 Withdrawals ‐ febuxostat 240 mg/day versus placebo, Outcome 1 TOTAL.
12.2
12.2. Analysis
Comparison 12 Withdrawals ‐ febuxostat 240 mg/day versus placebo, Outcome 2 Adverse event.
12.3
12.3. Analysis
Comparison 12 Withdrawals ‐ febuxostat 240 mg/day versus placebo, Outcome 3 Gout flare.
12.4
12.4. Analysis
Comparison 12 Withdrawals ‐ febuxostat 240 mg/day versus placebo, Outcome 4 Lack of efficacy.
12.5
12.5. Analysis
Comparison 12 Withdrawals ‐ febuxostat 240 mg/day versus placebo, Outcome 5 Other reasons.
13.1
13.1. Analysis
Comparison 13 Withdrawals ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 1 TOTAL.
13.2
13.2. Analysis
Comparison 13 Withdrawals ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 2 Adverse event.
13.3
13.3. Analysis
Comparison 13 Withdrawals ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 3 Gout flare.
13.4
13.4. Analysis
Comparison 13 Withdrawals ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 4 Lack of efficacy.
13.5
13.5. Analysis
Comparison 13 Withdrawals ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 5 Other reasons.
14.1
14.1. Analysis
Comparison 14 Withdrawals ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 1 TOTAL.
14.2
14.2. Analysis
Comparison 14 Withdrawals ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 2 Adverse event.
14.3
14.3. Analysis
Comparison 14 Withdrawals ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 3 Gout flare.
14.4
14.4. Analysis
Comparison 14 Withdrawals ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 4 Lack of efficacy.
14.5
14.5. Analysis
Comparison 14 Withdrawals ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 5 Other reasons.
15.1
15.1. Analysis
Comparison 15 Withdrawals ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 1 TOTAL.
15.2
15.2. Analysis
Comparison 15 Withdrawals ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 2 Adverse event.
15.3
15.3. Analysis
Comparison 15 Withdrawals ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 3 Gout flare.
15.4
15.4. Analysis
Comparison 15 Withdrawals ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 4 Lack of efficacy.
15.5
15.5. Analysis
Comparison 15 Withdrawals ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 5 Other reasons.
16.1
16.1. Analysis
Comparison 16 Withdrawals ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 1 TOTAL.
16.2
16.2. Analysis
Comparison 16 Withdrawals ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 2 Adverse event.
16.3
16.3. Analysis
Comparison 16 Withdrawals ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 3 Gout flare.
16.4
16.4. Analysis
Comparison 16 Withdrawals ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 4 Lack of efficacy.
16.5
16.5. Analysis
Comparison 16 Withdrawals ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 5 Other reasons.
17.1
17.1. Analysis
Comparison 17 Adverse events ‐ febuxostat 40 mg/day versus placebo, Outcome 1 TOTAL.
17.2
17.2. Analysis
Comparison 17 Adverse events ‐ febuxostat 40 mg/day versus placebo, Outcome 2 Serious.
17.3
17.3. Analysis
Comparison 17 Adverse events ‐ febuxostat 40 mg/day versus placebo, Outcome 3 Liver function test abnormalities.
17.4
17.4. Analysis
Comparison 17 Adverse events ‐ febuxostat 40 mg/day versus placebo, Outcome 4 Skin reaction.
17.5
17.5. Analysis
Comparison 17 Adverse events ‐ febuxostat 40 mg/day versus placebo, Outcome 5 Cardiovascular events (chest pain, coronary artery disease, myocardial infarction, atrial fibrillation).
17.6
17.6. Analysis
Comparison 17 Adverse events ‐ febuxostat 40 mg/day versus placebo, Outcome 6 Hypertension.
17.7
17.7. Analysis
Comparison 17 Adverse events ‐ febuxostat 40 mg/day versus placebo, Outcome 7 Diarrhea.
18.1
18.1. Analysis
Comparison 18 Adverse events ‐ febuxostat 80 mg/day versus placebo, Outcome 1 TOTAL.
18.2
18.2. Analysis
Comparison 18 Adverse events ‐ febuxostat 80 mg/day versus placebo, Outcome 2 Serious.
18.3
18.3. Analysis
Comparison 18 Adverse events ‐ febuxostat 80 mg/day versus placebo, Outcome 3 Liver function test abnormalities.
18.4
18.4. Analysis
Comparison 18 Adverse events ‐ febuxostat 80 mg/day versus placebo, Outcome 4 Skin reaction.
18.5
18.5. Analysis
Comparison 18 Adverse events ‐ febuxostat 80 mg/day versus placebo, Outcome 5 Cardiovascular events (chest pain, coronary artery disease, myocardial infarction, atrial fibrillation).
18.6
18.6. Analysis
Comparison 18 Adverse events ‐ febuxostat 80 mg/day versus placebo, Outcome 6 Hypertension.
18.7
18.7. Analysis
Comparison 18 Adverse events ‐ febuxostat 80 mg/day versus placebo, Outcome 7 Diarrhea.
19.1
19.1. Analysis
Comparison 19 Adverse events ‐ febuxostat 120 mg/day versus placebo, Outcome 1 TOTAL.
19.2
19.2. Analysis
Comparison 19 Adverse events ‐ febuxostat 120 mg/day versus placebo, Outcome 2 Serious.
19.3
19.3. Analysis
Comparison 19 Adverse events ‐ febuxostat 120 mg/day versus placebo, Outcome 3 Liver function test abnormalities.
19.4
19.4. Analysis
Comparison 19 Adverse events ‐ febuxostat 120 mg/day versus placebo, Outcome 4 Skin reaction.
19.5
19.5. Analysis
Comparison 19 Adverse events ‐ febuxostat 120 mg/day versus placebo, Outcome 5 Cardiovascular events (chest pain, coronary artery disease, myocardial infarction, atrial fibrillation).
19.6
19.6. Analysis
Comparison 19 Adverse events ‐ febuxostat 120 mg/day versus placebo, Outcome 6 Hypertension.
19.7
19.7. Analysis
Comparison 19 Adverse events ‐ febuxostat 120 mg/day versus placebo, Outcome 7 Diarrhea.
20.1
20.1. Analysis
Comparison 20 Adverse events ‐ febuxostat 240 mg/day versus placebo, Outcome 1 TOTAL.
20.2
20.2. Analysis
Comparison 20 Adverse events ‐ febuxostat 240 mg/day versus placebo, Outcome 2 Serious.
20.3
20.3. Analysis
Comparison 20 Adverse events ‐ febuxostat 240 mg/day versus placebo, Outcome 3 Liver function test abnormalities.
20.4
20.4. Analysis
Comparison 20 Adverse events ‐ febuxostat 240 mg/day versus placebo, Outcome 4 Skin reaction.
20.5
20.5. Analysis
Comparison 20 Adverse events ‐ febuxostat 240 mg/day versus placebo, Outcome 5 Cardiovascular events (chest pain, coronary artery disease, myocardial infarction, atrial fibrillation).
20.6
20.6. Analysis
Comparison 20 Adverse events ‐ febuxostat 240 mg/day versus placebo, Outcome 6 Hypertension.
20.7
20.7. Analysis
Comparison 20 Adverse events ‐ febuxostat 240 mg/day versus placebo, Outcome 7 Diarrhea.
21.1
21.1. Analysis
Comparison 21 Adverse events ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 1 TOTAL.
21.2
21.2. Analysis
Comparison 21 Adverse events ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 2 Serious.
21.3
21.3. Analysis
Comparison 21 Adverse events ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 3 Liver function test abnormalities.
21.4
21.4. Analysis
Comparison 21 Adverse events ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 4 Skin reaction.
21.5
21.5. Analysis
Comparison 21 Adverse events ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 5 Cardiovascular events (chest pain, coronary artery disease, myocardial infarction, atrial fibrillation).
21.6
21.6. Analysis
Comparison 21 Adverse events ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 6 Hypertension.
21.7
21.7. Analysis
Comparison 21 Adverse events ‐ febuxostat 40 mg/day versus allopurinol 200 or 300 mg/day, Outcome 7 Diarrhea.
22.1
22.1. Analysis
Comparison 22 Adverse events ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 1 TOTAL.
22.2
22.2. Analysis
Comparison 22 Adverse events ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 2 Serious.
22.3
22.3. Analysis
Comparison 22 Adverse events ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 3 Liver function test abnormalities.
22.4
22.4. Analysis
Comparison 22 Adverse events ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 4 Skin reaction.
22.5
22.5. Analysis
Comparison 22 Adverse events ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 5 Cardiovascular events (chest pain, coronary artery disease, myocardial infarction, atrial fibrillation).
22.6
22.6. Analysis
Comparison 22 Adverse events ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 6 Hypertension.
22.7
22.7. Analysis
Comparison 22 Adverse events ‐ febuxostat 80 mg/day versus allopurinol 200 or 300 mg/day, Outcome 7 Diarrhea.
23.1
23.1. Analysis
Comparison 23 Adverse events ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 1 TOTAL.
23.2
23.2. Analysis
Comparison 23 Adverse events ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 2 Serious.
23.3
23.3. Analysis
Comparison 23 Adverse events ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 3 Liver function test abnormalities.
23.4
23.4. Analysis
Comparison 23 Adverse events ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 4 Skin reaction.
23.5
23.5. Analysis
Comparison 23 Adverse events ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 5 Cardiovascular events (chest pain, coronary artery disease, myocardial infarction, atrial fibrillation).
23.6
23.6. Analysis
Comparison 23 Adverse events ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 6 Hypertension.
23.7
23.7. Analysis
Comparison 23 Adverse events ‐ febuxostat 120 mg/day versus allopurinol 300 mg/day, Outcome 7 Diarrhea.
24.1
24.1. Analysis
Comparison 24 Adverse events ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 1 TOTAL.
24.2
24.2. Analysis
Comparison 24 Adverse events ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 2 Serious.
24.3
24.3. Analysis
Comparison 24 Adverse events ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 3 Liver function test abnormalities.
24.4
24.4. Analysis
Comparison 24 Adverse events ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 4 Skin reaction.
24.5
24.5. Analysis
Comparison 24 Adverse events ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 5 Cardiovascular events (chest pain, coronary artery disease, myocardial infarction, atrial fibrillation).
24.6
24.6. Analysis
Comparison 24 Adverse events ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 6 Hypertension.
24.7
24.7. Analysis
Comparison 24 Adverse events ‐ febuxostat 240 mg/day versus allopurinol 300 mg/day, Outcome 7 Diarrhea.
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References

References to studies included in this review

Becker 2005a {published data only}
    1. Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. New England Journal of Medicine 2005;353(23):2450‐61. [PUBMED: 16339094] - PubMed
Becker 2005b {published data only}
    1. Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Palo WA, Eustace D, et alt L, Joseph‐Ridge N. Febuxostat, a Novel Nonpurine Selective Inhibitor ofXanthine Oxidase:a twenty‐eight‐day, multicenter, phase II, randomized, double‐blind, placebo‐controlled, dose‐response clinical trial examining safety and efficacy in patients with gout. Arthritis and Rheumatism 2005;52(3):916–23. [PUBMED: 15751090] - PubMed
    1. Goldfarb, D. S.MacDonald, P.Hunt, B.Gunawardhana, L. [Febuxostat in Gout: Serum Urate Responses in Uric Acid Overproducers vs. Underexcretors]. American Journal of Kidney Diseases. 2010; Vol. 55:B59. - PubMed
Becker 2009 {published data only}
    1. Becker MA, Schumacher HR, MacDonald PA, Lloyd E, Lademacher C. Clinical efficacy and safety of successful long‐term urate lowering with febuxostat or allopurinol in subjects with gout. Journal of Rheumatology 2009;36(6):1273‐82. - PubMed
Becker 2010 {published data only}
    1. Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E, Lademacher C. The urate‐lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Research and Therapy 2010;12(2):R63 Apr 6. [PUBMED: 20370912 ] - PMC - PubMed
    1. Whelton A, Becker MA, MacDonald P, Hunt B, Jackson RL. [Gout subjects with hyperuricemia and renal impairment treated withfebuxostat or allopurinol for 6 months]. International Journal of Rheumatic Diseases. 2010; Vol. 13:172‐7.
Schumacher 2008 {published data only}
    1. Schumacher HR Jr, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28‐week, phase III, randomized, double‐blind, parallel‐group trial. Arthritis and Rheumatism 2008;59(11):1540‐8. [PUBMED: 18975369] - PubMed
Schumacher 2009 {published data only}
    1. Schumacher HR, Becker MA, Lloyd E, MacDonald PA, Lademacher C. Febuxostat in the treatment of gout: 5‐yr findings of the FOCUS efficacy and safety study. Rheumatology 2009;48:188‐94. - PubMed

References to studies excluded from this review

Becker 2008 {published data only}
    1. Becker MA, MacDonald PA, Hunt BJ, Lademacher C, Joseph‐Ridge N. Determinants of the clinical outcomes of gout during the first year of urate‐lowering therapy. Nucleosides, Nucleotides & Nucleic Acids 2008;27(6):585‐91. - PubMed
Komoriya 2004 {published data only}
    1. Komoriya K, Hoshide S, Takeda K, Kobayashi H, Kubo J, Tsuchimoto M, et al. Pharmacokinetics and pharmacodynamics of febuxostat (TMX‐67), a non‐purine selective inhibitor of xanthine oxidase/xanthine dehydrogenase (NPSIXO) in patients with gout and/or hyperuricemia. Nucleosides, Nucleotides & Nucleic Acids 2004;23(8‐9):1119‐22. - PubMed

References to studies awaiting assessment

References to ongoing studies

NCT01078389 {unpublished data only}
    1. A Multicenter, Randomized, Double‐Blind, Phase 2 Study to Evaluate the Effect of Febuxostat Versus Placebo in Joint Damage in Hyperuricemic Subjects With Early Gout. Ongoing study March 2010.
NCT01082640 {unpublished data only}
    1. A Multicenter, Randomized, Double‐Blind, Phase 2 Study to Evaluate the Effect of Febuxostat Versus Placebo on Renal Function in Gout Subjects With Hyperuricemia and Moderate to Severe Renal Impairment. Ongoing study April 2010.
NCT01101035 {unpublished data only}
    1. A Multicenter, Randomized, Active‐Control, Phase 3B Study to Evaluate the Cardiovascular harms of Febuxostat and Allopurinol in Subjects With Gout and Cardiovascular Comorbidities. Ongoing study May 2010.

Additional references

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