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Ann Rheum Dis. 2017 May;76(5):811-820. doi: 10.1136/annrheumdis-2016-209213. Epub 2016 Nov 7.

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).

Author information

1
Rhumatologie, Lariboisière Hospital, and Université Paris Diderot Sorbonne Cité, Paris, France.
2
Division of Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA.
3
Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA.
4
Biometrics, Ardea Biosciences, Inc., San Diego, California, USA.
5
Research & Development, Ardea Biosciences, Inc., San Diego, California, USA.
6
Research & Development, AstraZeneca Pharmaceuticals, Gaithersburg, Maryland, USA.
7
Medical Affairs, Ardea Biosciences, Inc., San Diego, California, USA.
8
Service de rhumatologie, Université de Lausanne, Lausanne, Switzerland.

Abstract

OBJECTIVES:

Determine the efficacy and safety of daily lesinurad (200 or 400 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 ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 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 <6.0 mg/dL (<357 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±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 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 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 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 200 mg+allopurinol, in 9.5% of lesinurad 400 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 200 mg was generally well tolerated in patients with gout warranting additional therapy.

TRIAL REGISTRATION NUMBER:

NCT01493531.

KEYWORDS:

Gout; Inflammation; Outcomes research

PMID:
27821644
PMCID:
PMC5530336
DOI:
10.1136/annrheumdis-2016-209213
[Indexed for MEDLINE]
Free PMC Article

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