New urate-lowing therapies

New urate-lowing therapies Purpose of reviewTo discuss recent studies of lesinurad and arhalofenate.Recent findingsLesinurad acts by blocking urate reabsorption channels URAT-1 and OAT-4. It has urate-lowering effect when used alone and in combination with xanthine oxidase inhibitors (XOIs). Its uricosuric activity depends on glomerular filtration, and its’ efficacy is impaired at eGFR less than 30 ml/min. Lesinurad monotherapy (400 mg/day) associates with serum creatinine elevations. However, this risk is substantially attenuated with coprescription of a XOI and when prescribed at a dose of 200 mg/day. Given its’ modest urate-lowering effect, and the risk of serum creatinine elevation when used alone, it is licenced for use in combination with XOI for people unable to achieve target serum uric acid with XOI alone. Lesinurad does not have the drug interactions associated with probenecid, however, it is metabolized by CYP2C9, and should be used with caution if CYP2C9 inhibitors are coprescribed. Arhalofenate also acts by blocking URAT-1; however, it also blocks the NALP-3 inflammasome providing gout-specific anti-inflammatory effect. Arhalofenate has a weaker urate-lowering effect than lesinurad and further phase III evaluation is planned.SummaryLesinurad provides an additional option for people with gout unable to achieve target serum uric acid with XOI alone. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Opinion in Rheumatology Wolters Kluwer Health

New urate-lowing therapies

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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
ISSN
1040-8711
eISSN
1531-6963
D.O.I.
10.1097/BOR.0000000000000476
Publisher site
See Article on Publisher Site

Abstract

Purpose of reviewTo discuss recent studies of lesinurad and arhalofenate.Recent findingsLesinurad acts by blocking urate reabsorption channels URAT-1 and OAT-4. It has urate-lowering effect when used alone and in combination with xanthine oxidase inhibitors (XOIs). Its uricosuric activity depends on glomerular filtration, and its’ efficacy is impaired at eGFR less than 30 ml/min. Lesinurad monotherapy (400 mg/day) associates with serum creatinine elevations. However, this risk is substantially attenuated with coprescription of a XOI and when prescribed at a dose of 200 mg/day. Given its’ modest urate-lowering effect, and the risk of serum creatinine elevation when used alone, it is licenced for use in combination with XOI for people unable to achieve target serum uric acid with XOI alone. Lesinurad does not have the drug interactions associated with probenecid, however, it is metabolized by CYP2C9, and should be used with caution if CYP2C9 inhibitors are coprescribed. Arhalofenate also acts by blocking URAT-1; however, it also blocks the NALP-3 inflammasome providing gout-specific anti-inflammatory effect. Arhalofenate has a weaker urate-lowering effect than lesinurad and further phase III evaluation is planned.SummaryLesinurad provides an additional option for people with gout unable to achieve target serum uric acid with XOI alone.

Journal

Current Opinion in RheumatologyWolters Kluwer Health

Published: Mar 1, 2018

References

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