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Efficacy and safety of lesinurad for the treatment of hyperuricemia in gout.
Drugs Context 2019; 8:212581DC

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.

Authors+Show Affiliations

Rheumatology Division, Hospital de Cruces, Vizcaya, Spain.Department of Rheumatology, VieCuri Medisch Centrum, Venlo, The Netherlands.University Clinic, Dresden, Germany.Medical Affairs Department, Grünenthal Pharma, Aachen, Germany.Medical Affairs Department, Grünenthal Pharma, Aachen, Germany.Department of Rheumatology, Hôpital Laribroisiére, Paris, France.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31191704

Citation

Pérez-Ruiz, Fernando, et al. "Efficacy and Safety of Lesinurad for the Treatment of Hyperuricemia in Gout." Drugs in Context, vol. 8, 2019, p. 212581.
Pérez-Ruiz F, Jansen T, Tausche AK, et al. Efficacy and safety of lesinurad for the treatment of hyperuricemia in gout. Drugs Context. 2019;8:212581.
Pérez-Ruiz, F., Jansen, T., Tausche, A. K., Juárez-Campo, M., Gurunath, R. K., & Richette, P. (2019). Efficacy and safety of lesinurad for the treatment of hyperuricemia in gout. Drugs in Context, 8, p. 212581. doi:10.7573/dic.212581.
Pérez-Ruiz F, et al. Efficacy and Safety of Lesinurad for the Treatment of Hyperuricemia in Gout. Drugs Context. 2019;8:212581. PubMed PMID: 31191704.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of lesinurad for the treatment of hyperuricemia in gout. AU - Pérez-Ruiz,Fernando, AU - Jansen,Tim, AU - Tausche,Anne-Katrin, AU - Juárez-Campo,Mónica, AU - Gurunath,Ravichandra Karra, AU - Richette,Pascal, Y1 - 2019/05/29/ PY - 2019/02/06/received PY - 2019/04/16/revised PY - 2019/04/18/accepted PY - 2019/6/14/entrez PY - 2019/6/14/pubmed PY - 2019/6/14/medline KW - allopurinol KW - febuxostat KW - gout KW - hyperuricemia KW - lesinurad KW - serum uric acid levels KW - urate lowering KW - uric acid transporter 1 SP - 212581 EP - 212581 JF - Drugs in context JO - Drugs Context VL - 8 N2 - 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. SN - 1745-1981 UR - https://www.unboundmedicine.com/medline/citation/31191704/Efficacy_and_safety_of_lesinurad_for_the_treatment_of_hyperuricemia_in_gout L2 - http://dx.doi.org/10.7573/dic.212581 DB - PRIME DP - Unbound Medicine ER -