Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study.
OBJECTIVE
This 5-yr study assessed urate-lowering and clinical efficacy and safety of long-term febuxostat therapy in subjects with gout. The primary efficacy end-point was reduction to and maintenance of serum urate (sUA) levels < 6.0 mg/dl.


METHODS
Subjects who completed a previous 28-day study were entered into an open-label extension study and initially received febuxostat 80 mg daily. Between Weeks 4 and 24, dosing could be adjusted to febuxostat 40 or 120 mg. All subjects received gout flare prophylaxis during the first 4 weeks. Gout flares were recorded and treated throughout the study, and sUA, baseline tophi and safety were monitored.


RESULTS
Among 116 subjects initially enrolled, dose adjustments were made for 44 (38%) subjects. As a result, 8 subjects received febuxostat 40 mg, 79 received 80 mg, and 29 received 120 mg daily maintenance dose. At 5 yrs, 93% (54/58) of the remaining subjects had sUA < 6.0 mg/dl. Fifty-eight subjects (50%) discontinued prematurely; 38 did so in the first year. Thirteen subjects withdrew due to an adverse event. Sustained reduction of sUA was associated with nearly complete elimination of gout flares. In 26 subjects with a tophus at baseline, resolution was achieved in 69% (18/26) by last visit on study drug at any point during the study (Final Visit). There were no deaths reported during the study.


CONCLUSIONS
Long-term treatment with febuxostat resulted in durable maintenance of sUA < 6.0 mg/dl for most subjects. There was nearly complete abolition of gout flares in patients completing the study. Baseline tophi resolved in a majority of subjects.
Schumacher
H R
HR
VA Medical Center, 151K, University and Woodland Avenues, Philadelphia, PA 19104, USA. schumacr@mail.med.upenn.edu
Becker
M A
MA
Lloyd
E
E
MacDonald
P A
PA
Lademacher
C
C
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D017322:Clinical Trials, Phase II as Topic; D000069465:Febuxostat; D005260:Female; D005500:Follow-Up Studies; D006073:Gout / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D007596:Joints / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood; D055815:Young Adult
D015415:Biomarkers; D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid