治疗痛风和高尿酸血症药物研究进展

摘要/Abstract

摘要：

对急性痛风性关节炎的治疗，与常规剂量治疗方案相比，小剂量秋水仙碱或小剂量秋水仙碱+非甾体抗炎药治疗方案疗效相近，而安全性却大幅度提高。IL-1R拮抗剂阿那白滞素、利纳西普、康奈单抗等能有效缓解痛风急性期的症状，已成为第四类抗急性痛风的药物。别嘌呤醇的严重超敏反应综合征与肾功能、开始剂量、HLA-B*5801基因有关。非布司他、托匹司他、ulodesine、lesinurad、RDEA-3170、尿酸酶是近年来新型的降低尿酸药物。

关键词: 痛风, 高尿酸血症, 治疗药物, 研究进展

Abstract:

Compared with the conventional dose regimen, small dose of colchicine or small dose of colchicine and anti-inflammatory drug treatment show similar effect in treating acute gouty arthritis, while the safety is greatly improved. IL-1 receptor antagonists anakinra, rilonacept, and canakinumab can effectively alleviate the symptoms of acute phase of gout, and have become the fourth types of anti-acute gout drugs. The severe hypersensitivity syndrome of allopurinol is related to renal function, starting dose and HLA-B*5801 gene. Febuxostat, topiroxosta, ulodesine, lesinurad, RDEA-3170, uric acid enzyme are recently new drugs to reduce uric acid.

Key words: gout, hyperuricemia, therapeutic drug, research progress

中图分类号:

R589.7

陈光亮，周媛凤，张颖. 治疗痛风和高尿酸血症药物研究进展[J]. 中国临床药理学与治疗学, 2017, 22(1): 104-109.

CHEN Guangliang, ZHOU Yuanfeng, ZHANG Ying. Research progress in medicine for treating gout and hyperuricemia[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(1): 104-109.

参考文献

［1］Dalbeth N, Lauterio TJ, Wolfe HR. Mechanism of action of colchicine in the treatment of gout［J］. Clin Ther，2014,36(10):1465-1479.
［2］Terkeltaub RA , Furst DE, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study［J］.Arthritis Rheum，2010 ,62(4):1060-1068.
［3］蒙龙,李娟,龙锐,等.小剂量与常规剂量秋水仙碱治疗急性痛风性关节炎的系统评价［J］. 中国临床药理学与治疗学，2014,19(6):656-662.
［4］Khanna D,Khanna PP,Fitzgerald JD,et a1.2012 American College of Rheumatology guidelines for management of gout．Part 2:therapy and anti-inflammatory prophylaxis of acute gouty arthritis［J］. Arthritis Care Res(Hoboken)，2012,64(10):1447-14461.
［5］Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout［J］. Ann Rheum Dis，2016，pii: annrheumdis-2016-209707.
［6］中华医学会风湿病学分会. 2016中国痛风指南［J］.中华内科杂志, 2016,55(11):892-899.
［7］Terkeltaub RA.Colchicine update: 2008［J］. Semin Arthritis Rheum，2009,38(6):411-419.
［8］Terkeltaub RA,Furst DE, Digiacinto JL, et al. Novel evidence-based colchicines dose-reduction algorithm to predict and prevent colchicines toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors［J］. Arthritis Rheum，2011,63(8):2226-2237.
［9］Martinon F, Pétrilli V, Mayor A , et al. Gout-associated uric acid crystals activate the NALP3 infammasome［J］. Nature，2006, 440(7081): 237-241.
［10］Ottaviani S, Moltó A, Ea HK, et al. Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases［J］. Arthritis Res Ther, 2013, 15(5): R123.
［11］Chen K, Fields T, Mancuso CA, et al. Anakinra's efficacy is variable in refractory gout: report of ten cases［J］. Semin Arthritis Rheum,2010, 40(3): 210-214.
［12］Terkeltaub R, Sundy JS, Schumacher HR, et al. The intedeukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequenee crossover, non-randomised, single-blind pilot study［J］. Ann Rheum Dis, 2009, 68(10):1613-1617.
［13］Terkeltaub RA, Schumacher HR, Carter JD, et al.Rilonacept in the treatment of acute gouty arthritis: a randomized, controlled clinical trial using indomethacin as the active comparator［J］. Arthritis Res Ther,2013,15(1):R25.
［14］Mitha E, Schumacher HR, Fouche L, et al. Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial［J］. Rheumatology (Oxford), 2013, 52(7):1285-1292.
［15］Schlesinger N. Canakinumab in gout［J］. Expert Opin Biol Ther,2012,12(9):1265-1275.
［16］Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions［J］. Ann Rheum Dis,2012,71(11):1839-1848.
［17］Bardin T. Canakinumab for the patient with difficult-to-treat gouty arthritis: review of the clinical evidence［J］. Joint Bone Spine,2015,82 Suppl 1:eS9-16.
［18］Stamp LK, Taylor WJ, Jones PB, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol［J］. Arthritis Rheum,2012,64(8):2529-2536.
［19］汪琳,邱晓燕.119例重症药疹的回顾性分析［J］.中国临床药理学与治疗学,2014,19(8): 885-889.
［20］中华医学会内分泌学分会.高尿酸血症和痛风治疗的中国专家共识［J］.中华内分泌代谢杂志, 2013,29(11):913-920.
［21］Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study［J］. Ann Rheum Dis,2013,72(6):826-830.
［22］ Reinders MK, Haagsma C, Jansen TL, et al. A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout［J］. Ann Rheum Dis,2009,68(6):892-897.
［23］Fleischmann R, Kerr B, Yeh LT, et al.Pharmacodynamic, pharmacokinetic and tolerability evaluation concomitant administration of lesinuradand febuxostat in gout patients with hyperuricaemia［J］. Rheumatology, 2014, 53(12):2167-2174.
［24］Hair PI,McCormack PL,Keating GM. Febuxostat［J］. Drugs, 2008,68(13):1865-1874.
［25］Li S, Yang H, Guo Y, et al. Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: a systematic review and network meta-analysis［J］. Sci Rep, 2016,6:33082. doi: 10.1038/srep33082.
［26］Chohan S. Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions［J］.J Rheumatol, 2011,38(9):1957-1959.
［27］Bardin T, Chalès G, Pascart T, et al. Risk of cutaneous adverse events with febuxostat treatment in patients with skin reaction to allopurinol. A retrospective,hospital-based study of 101 patients with consecutive allopurinol and febuxostat treatment［J］. Joint Bone Spine,2016, 83(3):314-317.
［28］Hosoya T,Sasaki T,Hashimoto H,et al.Clinical efficacy and safety of topiroxostat in Japanese male hyperuricemic patients with or without gout: an exploratory, phase 2a, multicentre, randomized, double-blind, placebo-controlled study［J］. J Clin Pharm Ther,2016,41(3):298-305.
［29］Hosoya T, Ogawa Y, Hashimoto H, et al. Comparison of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout: a phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study［J］.J Clin Pharm Ther, 2016,41(3):290-297.
［30］Hosoya T,Ohno I, Nomura S, et al. Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout［J］. Clin Exp Nephrol,2014,18(6):876-884.
［31］Becker M, Hollister A, Terkeltaub R, et al. BCX4208 added to allopurinol increases response rates in patients with gout who fail to reach goal range serum uric acid on allopurinol alone: a randomized, double-blind, placebo-controlled trial［J］. Ann Rheum Dis,2013,71:438.
［32］Hollister A, Dobo S, Maetzel A, et al. Long-term safety of BCX4208 added to allopurinol in the chronic management of gout: results of a phase 2 24-week blinded safety extension and vaccine challenge study［J］. Ann Rheum Dis,2013,71:442-443.
［33］Fleischmann R,Kerr B,Yeh LT, et al. Pharmacodynamic, pharmacokinetic and tolerability evaluation of concomitant administration of lesinurad and febuxostat in gout patients with hyperuricaemia［J］. Rheumatology (Oxford), 2014,53(12):2167-2174.
［34］Saag KG, Fitz-Patrick D, Kopicko J,et al.Lesinurad combined with allopurinol: randomized, double-blind, placebo-controlled study in gout subjects with inadequate response to standard of care allopurinol (A US-based Study) ［J］. Arthritis Rheumatol,2016 Aug 26. doi: 10.1002/art.39840. ［Epub ahead of print］
［35］Bardin T, Keenan R,Khanna P, et al. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with allopurinol: results from a phase III study in gout patients having an inadequate response to standard of care (clear 2) ［J］. Ann Rheum Dis, 2015,74: 545.
［36］Perez-Ruiz F,Sundy JS, Miner JN, et al. Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol［J］. Ann Rheum Dis,2016,75(6):1074-1080.
［37］Thomson reuters cortellis ［DB/OL］. ［2015-01-05］. https://cortellis.thomsonreuterslifesciences.com.
［38］Digumarti R, Sinha S, Nirni SS,et al. Efficacy of rasburicase (recombinant urate oxidase) in the prevention and treatment of malignancy-associated hyperuricemia: an Indian experience［J］. Indian J Cancer,2014,51(2):180-183.
［39］Vadhan-Raj S, Fayad LE, Fanale MA, et al. A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome［J］. Ann Oncol, 2012, 23(6):1640-1645.
［40］Trifilio SM,Pi J,Zook J,et al.Effectiveness of a single 3-mg rasburicase dose for the management of hyperuricemia in patients with hematological malignancies［J］.Bone Marrow Transplant, 2010,18(1):60-63.
［41］Pegloticase. An excessively dangerous and inadequately evaluated hypouricaemic drug［J］. Prescrire Int,2014,23(151):173-176.
［42］Lipsky PE, Calabrese LH, Kavanaugh A, et al. Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout［J］. Arthritis Res Ther,2014,16(2):R60.
［43］Patel KS, Lau JE, Zembillas AS, et al.Single 4.5 mg fixed-dose of rasburicase for hyperuricemia associated with tumor lysis syndrome［J］. J Oncol Pharm Pract, 2016 Apr 15. pii: 1078155216644975. ［Epub ahead of print］

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