Efficacy and safety of lesinurad for the treatment of hyperuricemia in gout

Article Page

Abstract

The aim of this review is to present current evidence about the efficacy and safety of lesinurad in combination with xanthine oxidase inhibitors (XOIs) in the treatment of hyperuricemia in patients with gout. Gout is the most common inflammatory form of arthritis. It is caused by an elevated concentration of serum uric acid (UA) that leads to the formation of monosodium urate crystals in joints and different tissues. The goal of therapy is to maintain serum UA levels at <6 mg/dL (0.36 mmol/L), to prevent the formation and deposition of monosodium urate crystals, and to dissolve existing crystals. Lesinurad, a new uricosuric, increases renal urate excretion by selectively inhibiting the renal uric acid transporter 1 (URAT1). Lesinurad is indicated in adults, in combination with a XOI, for the adjunctive treatment of hyperuricemia in patients with gout (with or without tophi) who have not achieved target serum UA levels with an adequate dose of a XOI alone. With the combination strategy, serum UA targets could be reached with the consequence of inhibiting formation of new crystals and promoting dissolution of existing crystals and, therefore, inducing improvement of outcomes such as flares and tophi. The approval of lesinurad was based on data from three pivotal phase III studies (CLEAR 1, CLEAR 2, and CRYSTAL). These clinical studies assessed lesinurad 200 and 400 mg doses. As only lesinurad 200 mg/day dose was finally approved and commercialized, it will be the focus of this paper. In the pivotal clinical trials, the target serum UA level was achieved by significantly more patients in lesinurad 200 mg plus allopurinol group (CLEAR 1 and CLEAR 2 trials) or lesinurad 200 mg plus febuxostat group (CRYSTAL study) compared with patients who received either XOI alone. In these trials, the safety profile of lesinurad 200 mg plus a XOI was comparable to allopurinol or febuxostat alone. Lesinurad, in combination with a XOI, is an effective and safe treatment that covers unmet needs in adults with gout who have not achieved target serum UA levels with a XOI alone.

Keywords: allopurinol, febuxostat, gout, hyperuricemia, lesinurad, serum uric acid levels, urate lowering, uric acid transporter 1.

Citation: Pérez-Ruiz F, Jansen T, Tausche A-K, Juárez-Campo M, Karra Gurunath R, Richette P. Efficacy and safety of lesinurad for the treatment of hyperuricemia in gout. Drugs in Context 2019; 8: 212581. DOI: 10.7573/dic.212581

Contributions: All authors contributed equally to the preparation of this review. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: Dr Perez Ruiz reports personal fees from Menarini, personal fees from Grunenthal, and personal fees from Horizon, outside the submitted work. Dr Tim Jansen reports research support from Ardea/Olatec, lecture fees from Grunenthal, and consultancy fees from Abbvie/Astra-Zeneca/Celgene/Novartis. Mónica Juárez and Ravichandra Karra Gurunath are full-time employees in the Medical Affairs Department from Grünenthal Pharma. Dr Anne-Kathrin Tausche received personal fees from Berlin Chemie- Menarini, AstraZeneca/Ardea Biosciences, and Grünenthal Pharma. Dr Pascal Richette received fees from Ipsen, Menarini, Savient, Grunenthal, and AstraZeneca. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at https://www.drugsincontext.com/wp-content/uploads/2019/04/dic.212581-COI.pdf

Acknowledgements: Writing and editorial assistance in the preparation of this review article was provided by Content Ed Net (Madrid).

Funding declaration: Editorial assistance was provided by Content Ed Net (Madrid) with funding from Grünenthal Pharma. There was no other funding associated with the preparation of this article.

Copyright: Copyright © 2019 Pérez-Ruiz F, Jansen T, Tausche A-K, Juárez-Campo M, Karra Gurunath R, Richette P. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2019 Pérez-Ruiz F, Jansen T, Tausche A-K, Juárez-Campo M, Karra Gurunath R, Richette P. https://doi.org/10.7573/dic.212581. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/efficacy-and-safety-of-lesinurad-for-the-treatment-of-hyperuricemia-in-gout

Correspondence: Fernando Pérez-Ruiz, Hospital de Cruces, Plaza de Cruces, S/N, 48903 Baracaldo, Vizcaya, Spain. fperezruiz@telefonica.net

Provenance: submitted; externally peer reviewed.

Submitted: 6 February 2019; Peer review comments to author: 3 March 2019; Revised manuscript received: 16 April 2019; Accepted: 18 April 2019; Publication date: 29 May 2019.

Drugs in Context is published by BioExcel Publishing Ltd. Registered office: Plaza Building, Lee High Road, London, England, SE13 5PT.

BioExcel Publishing Limited is registered in England Number 10038393. VAT GB 252 7720 07.

For all manuscript and submissions enquiries, contact the Editor-in-Chief gordon.mallarkey@bioexcelpublishing.com

For all permissions, rights and reprints, contact David Hughes david.hughes@bioexcelpublishing.com

Download free full text PDF