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Lesinurad: A Review in Hyperuricaemia of Gout

Abstract

Lesinurad (Zurampic®) is an oral selective inhibitor of the URAT1 and OAT4 uric acid (UA) transporters of the kidney, via which it inhibits UA reabsorption and thus increases renal UA excretion and lowers serum UA (sUA) levels. Lesinurad 200 mg once daily is indicated for use in combination with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in adults with gout who have not achieved target sUA levels with an XOI alone. Approval was based on three 12-month phase 3 trials that evaluated lesinurad in combination with allopurinol in adults with gout inadequately responsive to allopurinol (CLEAR 1 and 2) and in combination with febuxostat in adults with tophaceous gout (CRYSTAL). The target sUA level of <6 mg/dL at 6 months (primary endpoint) was achieved by significantly more lesinurad plus allopurinol than placebo plus allopurinol recipients in the CLEAR trials. In CRYSTAL (which enrolled patients regardless of prior XOI experience, and included 3 weeks of febuxostat before randomization), the proportion of patients who achieved an sUA target of <5 mg/dL did not reach statistical significance between lesinurad plus febuxostat and placebo plus febuxostat at 6 months (primary endpoint), although significantly favoured the lesinurad plus febuxostat group at 12 months. Notably, the sUA target of <5 mg/dL at 6 months was met with lesinurad plus febuxostat in the CRYSTAL subgroup that had uncontrolled hyperuricaemia at baseline, despite having received febuxostat pre-randomization. Lesinurad plus XOI regimens were generally not associated with improvements in flares and tophi in these trials, although clinical benefit became more apparent in 12-month extension studies; the regimens were also generally well tolerated. Thus, lesinurad, in combination with an XOI, is an emerging option for the treatment of hyperuricaemia in adults with gout who have not achieved target sUA levels with an XOI alone.

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Acknowledgements

During the peer review process, the manufacturer of lesinurad was offered the opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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Correspondence to Emma D. Deeks.

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The preparation of this review was not supported by any external funding.

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Emma Deeks is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

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The manuscript was reviewed by: S. Chohan, Arizona Arthritis and Rheumatology Associates, Phoenix, AZ, USA; A. L. Gaffo, University of Alabama at Birmingham and Rheumatology Section, Birmingham VA Medical Center, Birmingham, AL, USA; P. Khanna, Medicine-Rheumatology, University of Michigan, Ann Arbor, MI, USA.

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Deeks, E.D. Lesinurad: A Review in Hyperuricaemia of Gout. Drugs Aging 34, 401–410 (2017). https://doi.org/10.1007/s40266-017-0461-y

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Keywords

  • Chronic Kidney Disease
  • Uric Acid
  • Gout
  • Allopurinol
  • Febuxostat