Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study).
Ann Rheum Dis
; 76(5): 811-820, 2017 May.
Article
in En
| MEDLINE
| ID: mdl-27821644
ABSTRACT
OBJECTIVES:
Determine the efficacy and safety of daily lesinurad (200 or 400â mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial.METHODS:
Patients on allopurinol ≥300â mg (≥200â mg in moderate renal impairment) had sUA level of ≥6.5â mg/dL (≥387â µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0â mg/dL (<357â µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data.RESULTS:
Patients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90â years, gout duration 11.5±9.26â years and baseline sUA of 6.9±1.2â mg/dL (410±71â µmol/L). Lesinurad at 200 and 400â mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200â mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200â mg+allopurinol, 15.0% of lesinurad 400â mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200â mg+allopurinol, in 9.5% of lesinurad 400â mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively.CONCLUSION:
Lesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200â mg was generally well tolerated in patients with gout warranting additional therapy. TRIAL REGISTRATION NUMBER NCT01493531.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Thioglycolates
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Triazoles
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Uricosuric Agents
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Allopurinol
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Gout Suppressants
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Gout
Type of study:
Clinical_trials
Limits:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Language:
En
Year:
2017
Type:
Article