Integrated safety studies of the urate reabsorption inhibitor lesinurad in treatment of gout.
Rheumatology (Oxford)
; 58(1): 61-69, 2019 01 01.
Article
in En
| MEDLINE
| ID: mdl-30124941
ABSTRACT
Objective:
Lesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy.Methods:
Safety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years).Results:
In the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals.Conclusion:
At the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thioglycolates
/
Triazoles
/
Cardiovascular Diseases
/
Gout Suppressants
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Enzyme Inhibitors
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Gout
/
Kidney Diseases
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
Journal:
Rheumatology (Oxford)
Journal subject:
REUMATOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
United States