Journal article
Integrated safety studies of the urate reabsorption inhibitor lesinurad in treatment of gout
Rheumatology (Oxford, England), Vol.58(1), pp.61-69
01/01/2019
DOI: 10.1093/rheumatology/key245
PMCID: PMC6293483
PMID: 30124941
Abstract
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.
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).
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.
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.
Details
- Title: Subtitle
- Integrated safety studies of the urate reabsorption inhibitor lesinurad in treatment of gout
- Creators
- Robert Terkeltaub - VA San Diego Healthcare SystemKenneth G Saag - University of Alabama at BirminghamDavid S Goldfarb - New York UniversityScott Baumgartner - Ironwood PharmaceuticalsBruce M Schechter - Ironwood PharmaceuticalsRitu Valiyil - Ironwood PharmaceuticalsDiana Jalal - University of IowaMichael Pillinger - New York UniversityWilliam B White - University of Connecticut
- Resource Type
- Journal article
- Publication Details
- Rheumatology (Oxford, England), Vol.58(1), pp.61-69
- DOI
- 10.1093/rheumatology/key245
- PMID
- 30124941
- PMCID
- PMC6293483
- ISSN
- 1462-0324
- eISSN
- 1462-0332
- Grant note
- P50 AR060772 / NIAMS NIH HHS I01 BX001660 / BLRD VA
- Language
- English
- Date published
- 01/01/2019
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359822102771
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