New possibilities of uratedecreasing therapy in patients with arthrolithiasis


DOI: https://dx.doi.org/10.18565/therapy.2018.7-8.111-118

M.S. Petrova, M.M. Musiichuk, O.V.Inamova, V.I. Mazurov

1 The Department of therapy and rheumatology named after Ae.Ae. Aeikhvald of Federal state budgetary institution of higher education I.I. Mechnikov North-Western state medical university, St.Peterburg; 2 Federal state budgetary institution Clinical hospital of rheumatology №25, St.Peterburg; 3 State clinical centre of arthrolithiasis, St.Petersburg
Febuxostat is a newly appeared on the Russian pharmaceutical market arthrifuge remedy; it is non-purine, selective inhibitor of isoforms of xanthineoxidoreductase (XOR), its action is aimed at the reduction of uric acid (UA) level in blood serum. The pharmacokinetic properties of febuxostat do not depend on renal clearance, which differs it from allopurinol and could be considered to be an advantage in the treatment of chronic renal disease patients. In a row of research studies, a further evaluation of the safety of febuxostat relatively to the cardiovascular system is performed, as well as its positive impact on the preservation of kidney function. Febuxostat more significantly suppresses XOR than allopurinol, which is confirmed by more frequent achievement of the target UA level, especially in patients with a high concentration of urates in blood serum. It is also important that elderly patients do not require the correction of febuxostat dose.
Keywords: arthrolithiasis, hyperuricemia, febuxostat, allopurinol, chronic renal diseases, cardiovascular diseases
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Literature

  • Smith E.U.R., Diaz-Torne C., Perez-Ruiz F. et al. Epidemiology of gout: an update. Best Pract. Res. Clin. Rheumatol. 2010;24:811–27.
  • Kuo C.F., Grainge M.J., Zhang W. et al. Global epidemiology of gout: prevalence, incidence and risk factors. Nat. Rev. Rheumatol. 2015 Jul 7. doi: 10.1038/nrrheum.2015.91. [Epub ahead of print].
  • Hak A.E., Curhan G.C., Grodstein F. et al. Menopause, postmenopausal hormone use and risk of incident gout. Ann. Rheum. Dis. 2010;69:1305–9.
  • Smith E., Hoy D., Cross M. et al. The global burden of gout: estimates from the Global Burden of Disease 2010 study. Ann. Rheum. Dis. 2014;73(8):1470–6.
  • Vos T., Barber R.M., Bell B. et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990- 2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Jun 7. pii: S0140-6736(15)60692-4.
  • Zhu Y., Pandya B.J., Choi H.K. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136–41.
  • Lawrence R.C., Felson D.T., Helmick C.G. et al. National Arthritis Data Wo. Arthritis Rheum. 2008;58(1):26–35. Downloaded by [University of California, San Diego] at 06:48 07 March 2016.
  • Kuo C.F., Grainge M.J., Mallen C. et al. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann. Rheum. Dis. 2015;74(4):661–7.
  • Mikuls T.R., Farrar J.T., Bilker W.B. et al. Gout epidemiology: results from the UK General Practice Research Database, 1990-1999. Ann. Rheum. Dis. 2005;64(2):267–72.
  • Fravel M.A., Ernst M.E. Management of gout in the older adult. Am. J. Geriatr.Pharmacother. 2011;9(5):271–85.
  • Winnard D., Wright C., Taylor W.J. et al. National prevalence of gout derived from administrative health data in Aotearoa New Zealand. Rheumatology. 2012;51:901–9.
  • Doherty M., Jansen T.L., Nuki G. et al. Gout: why is this curable disease so seldom cured? Ann. Rheum. Dis. 2012;71(11):1765–70.
  • Singh J.A., Hodges J.S., Toscano J.P. et al. Quality of care for gout in the US needs improvement. Arthr. Rheum. 2007;57: 822–9.
  • Perez-Ruiz F., Dalbeth N., Bardin T. A review of uric acid, crystal deposition disease, and gout. Adv. Ther. 2015;32(1):31–41.
  • Edwards N.L., Sundy J.S., Forsythe A. et al. Work productivity loss due to flares in patients with chronic gout refractory to conventional therapy. J. Med. Econ. 2011;14(1):10–5.
  • Richette P., Doherty M., Pascual E. et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann. Rheum. Dis. 2017;76:29–42.
  • Richette P., Perez-Ruiz F., Doherty M. et al. Improving cardiovascular and renal outcomes in gout: what should we target? Nat. Rev. Rheumatol. 2014;10(11):654–61.
  • Rees F., Hui M., Doherty M. Optimizing current treatment of gout. Nat. Rev. Rheumatol. 2014;10(5):271–83.
  • Zhang W., Doherty M., Bardin T. et al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee For International Clinical Studies Including Therapeutics (ESCISIT). Ann. Rheum. Dis. 2006;65(10)1312–24.
  • Khanna D., Khanna P.P., Fitzgerald J.D. et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthr. Care Res. (Hoboken). 2012;64(10):1447–61.
  • Richette P., Bardin T. Gout. Lancet. 2010;375(9711):318–28.
  • Beara-Lasic L., Pillinger M.H., Goldfarb D.S. Advances in the management of gout: critical appraisal of febuxostat in the control of hyperuricemia. Int. J. Nephrol. Renovasc. Dis. 2010;3:1–10.
  • Seth R., Kydd A.S., Buchbinder R. et al. Allopurinol for chronic gout. Cochrane Database Syst. Rev. 2014 Oct 14;10:CD006077.
  • Kydd A.S., Seth R., Buchbinder R. et al. Uricosuric medications for chronic gout. Cochrane Database Syst. Rev. 2014 Nov 14;11:CD010457.
  • Castrejon I., Toledano E., Rosario M.P. et al. Safety of allopurinol compared with other uratelowering drugs in patients with gout: a systematic review and meta-analysis. Rheumatol. Int. 2015;35(7):1127–37.
  • Diaz-Tor.né C, Perez-Herrero N., Perez-Ruiz F. New medications in development for the treatment of hyperuricemia of gout. Curr. Opin. Rheumatol. 2015;27(2):164–9. hyperuricemia of gout. Future Rheumatol. 10/2008; 3(5):421-427.
  • Okamoto K., Eger B.T., Nishino T. et al. An extremely potent inhibitor of xanthine oxidoreductase. J. Biol. Chem. 2003;278:1848–55.
  • The vision of Febuxostat. Teijin Pharma Limited. Project stories. Japan. 2013;01. Available at: http://www.teijin-pharma.com/project/story01.html [Last accessed 23 August 2015].
  • Adenuric. European Medicines Agency. Human medicines. Authorisation details. United Kingdom, 2015. [Last accessed 19 August 2015].
  • Uloric U.S. Food and Drug Administration. Drug approval package. United States, 2009. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000toc.cfm [Last accessed 19 August 2015].
  • The Pharmaceuticals and Medical Devices Agency annual report FY 2010. Japan. 2011;147.
  • Uloric. Full prescribing information. U.S. Food and Drug Administration. U.S. 2012;2.
  • Adenuric. Summary of product characteristics. European Medicines Agency. United Kingdom, 2015. P. 2.
  • Perez-Ruiz F., Punzi L. Hyperuricemia and tissue monourate deposits: prospective therapeutic considerations. Eur. Rev. Med. Pharmacol. Sci. 2015;19 (9):1549–52.
  • Adenuric. Public Summary Document. Pharmaceutical Benefits Advisory Committee. Australia, 2015. P. 1.
  • Japanese Society of Gout and Nucleic Acid Metabolism. Digest of Guideline for the Management of Hyperuricemia and Gout: second edition. Gout Nucl Acid Met. 2010;34 (1):109–44.
  • Zyloprim. U.S. Food and Drug Administration. Drugs@FDA. U.S. 2015. [Last accessed 19 August 2015].
  • Takano Y., Hase-Aoki K., Horiuchi H. et al. Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase. Life Sci. 2005;76(16):1835–47.
  • Okamoto K., Eger B.T., Nishino T. et al. An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition. J. Biol. Chem. 2003;278(3):1848–55.
  • Osada Y., Tsuchimoto M., Fukushima H. et al. Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodents. Eur. J. Pharmacol. 1993;241(2–3):183–8.
  • Khosravan R., Grabowski B.A., Wu J.T. et al. Pharmacokinetics, pharmacodynamics and safety of febuxostat, a non-purine selective inhibitor of xanthine oxidase, in a dose escalation study in healthy subjects. Clin. Pharmacokinet. 2006;45(8):821–41.
  • Khosravan R., Grabowski B., Wu J.T. et al. Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects. Br. J. Clin. Pharmacol. 2008;65(3):355–63.
  • Zhang M., DI X., Xu L. et al. Pharmacokinetics and pharmacodynamics of febuxostat under fasting conditions in healthy individuals. Exp. Ther. Med. 2014;7(2):393–6.
  • Komoriya K., Hoshide S., Takeda K. et al. Pharmacokinetics and pharmacodynamics of febuxostat (TMX-67), a non-purine selective inhibitor of xanthine oxidase/xanthine Downloaded by [University of California, San Diego] at 06:48 07 March 2016 dehydrogenase (NPSIXO) in patients with gout and/or hyperuricemia. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1119–22.
  • Khosravan R., Wu J.T., Joseph-Ridge N. et al. Pharmacokinetic interactions of concomitant administration of febuxostat and NSAIDs. J. Clin. Pharmacol. 2006;46(8):855–66.
  • Mukoyoshi M., Nishimura S., Hoshide S. et al. In vitro drug-drug interaction studies with febuxostat, a novel non-purine selective inhibitor of xanthine oxidase: plasma protein binding, identification of metabolic enzymes and cytochrome P450 inhibition. Xenobiotica. 2008;38(5):496–510
  • Grabowski B., Khosravan R., Wu J.T. et al. Effect of hydrochlorothiazide on the pharmacokinetics and pharmacodynamics of febuxostat, a non-purine selective inhibitor of xanthine oxidase. Br. J. Clin. Pharmacol. 2010;70(1):57–64.
  • Hoshide. S, Takahashi Y., Ishikawa T. et al. PK/PD and safety of a single dose of TMX-67 (febuxostat) in subjects with mild and moderate renal impairment. Nucleosides Nucleotides Nucleic Acids. 2004;23(8–9):1117–8.
  • Mayer M.D., Khosravan R., Vernillet L. et al. Pharmacokinetics and pharmacodynamics of febuxostat, a new non-purine selective inhibitor of xanthine oxidase in subjects with renal impairment. Am. J. Ther. 2005;12(1):22–34.
  • Khosravan R., Grabowski B.A., Mayer M.D. et al. The effect of mild and moderate hepatic impairment on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase. J. Clin. Pharmacol. 2006;46(1):88–102.
  • Khosravan R., Kukulka M.J., Wu J.T. et al. The effect of age and gender on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase. J. Clin. Pharmacol. 2008;48(9):1014–24. Downloaded by [University of California, San Diego] at 06:48 07 March 2016.
  • Doré M., Frenette A.J., Mansour A.M. et al. Febuxostat as a novel option to optimize thiopurines’ metabolism in patients with inadequate metabolite levels. Ann. Pharmacother. 2014;48(5):648–51.
  • Febuxostat. ClincalTrials.gov. United States, 2015. Available at: https://clinicaltrials.gov/ct2/results?term=febuxostat&pg=1 [Last accessed 23 August 2015].
  • Febuxostat. International Clinical Trials Registry Platform. World Health organization, 2015. Available at: http://apps.who.int/trialsearch/default.aspx [Last accessed 25 August 2015].
  • Tayar J.H., Lopez-Olivo M.A., Suarez-Almazor M.E. Febuxostat for treating chronic gout. Cochrane Database Syst. Rev. 2012 Nov 14;11:CD008653.
  • Gray C.L., Walters-Smith N.E. Febuxostat for treatment of chronic gout. Am. J. Health Syst. Pharm. 2011;68(5):389–98.
  • Becker M.A., Schumacher H.R., Wortmann R.L. et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N. Engl. J. Med. 2005;353:2450–61.
  • Becker M.A., Schumacher H.R., Wortmann R.L, et al. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight day, multicenter, phase II, randomized, doubleblind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout. Arthr. Rheum. 2005;52:916–23.
  • Schumacher H.R., Becker M.A., Wortmann R.L. et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthr. Rheum. 2008;59:1540–8. Downloaded by [University of California, San Diego] at 06:48 07 March 2016.
  • Becker M.A., Schumacher H.R., Espinoza L.R. et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthr. Res. 2010;12:R63.
  • Schumacher H.R., Becker M.A., Lloyd E. et al. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy study. Rheumatology. 2009;48:188–94.
  • Becker M.A., Schumacher H.R., MacDonald P.A. et al. Clinical efficacy and safety of successful long-term urate lowering with febuxostat or allopurinol in subjects with gout. J. Rheumatol. 2009;36:1273–82.
  • Kamatani N., Fujimori S., Hada T. et al. Placebo-controlled double-blind dose-response study of the non-purine-selective xanthine oxidase inhibitor febuxostat (TMX-67) in patients with hyperuricemia (including gout patients) in japan: late phase 2 clinical study. J. Clin. Rheumatol. 2011;17(4 Suppl. 2):35–43.
  • Sung Oh Ahn, Shuichi Ohtomo, Jumpei Kiyokawa, Toshito Nakagawa, Mizuki Yamane, Kyoung June Lee, Ki Hwan Kim, Byung Ho Kim, Jo Tanaka, Yoshiki Kawabe, and Naoshi HoribaStronger Uricosuric Effects of the Novel Selective URAT1 Inhibitor UR-1102 Lowered Plasma Urate in Tufted Capuchin Monkeys to a Greater Extent than Benzbromarones. J. Pharmacol. Exp. Ther. 2016;357:157–66. Copyright ª 2016. Am. Soc. Pharmacol. Exp. Ther.
  • Kamatani N., Fujimori S., Hada T. et al. An allopurinol-controlled, randomized, double-dummy, double-blind, parallel between-group, comparative study of febuxostat (TMX-67), a nonpurine- selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study. J. Clin. Rheumatol. 2011;17(4 Suppl. 2):13–8.
  • Kamatani N., Fujimori S., Hada T. et al. Placebo-controlled, double-blind study of the nonpurine- selective xanthine oxidase inhibitor Febuxostat (TMX-67) in patients with Downloaded by [University of California, San Diego] at 06:48 07 March 2016 hyperuricemia including those with gout in Japan: phase 3 clinical study. J. Clin. Rheumatol. 2011;17(4 Suppl. 2):19–26.
  • Perez-Ruiz F., Chinchilla S., Atxotegi J. et al. Rheumatol. Intern. 2015;35(11):1857–61.
  • MacDonald T.M., Ford I., Nuki G. et al. Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia. BMJ. Open. 2014;4(7):e005354.
  • White W.B., Chohan S., Dabholkar A. et al. Cardiovascular safety of febuxostat and allopurinol in patients with gout and cardiovascular comorbidities. Am. Heart J. 2012;164(1):14–20.
  • Sánchez-Lozada L.G., Tapia E., Soto V. et al. Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia. Nephrol. Dial. Transplant. 2008;23(4):1179–85.
  • Whelton A., Macdonald P.A., Zhao L. et al. Renal function in gout: long-term treatment effects of febuxostat. J. Clin. Rheumatol. 2011;17(1):7–13.
  • Hosoya T., Kimura K., Itoh S. et al. The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multicenter randomized controlled study. Trials. 2014 ;15:26.
  • Sircar D., Chatterjee S., Waikhom R. et al. Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia: A 6-Month, Double-Blind, Randomized, Placebo-Controlled Trial. Am. J. Kidney Dis. 2015. Doi: 10.1053/j.ajkd.2015.05.017. Downloaded by [University of California, San Diego] at 06:48 07 March 2016.
  • Sofue T., Inui M., Hara T, et al. Efficacy and safety of febuxostat in the treatment of hyperuricemia in stable kidney transplant recipients. Drug Des.Deliv. Ther. 2014;8:245– 53.


    • About the Autors

    Marianna S. Petrova, PhD, head of the State clinical centre of arthrolithiasis, associate professor of the Department of therapy and Rheumatology named after Ae.Ae. Aeikhvald of Federal state budgetary institution of higher education I.I. Mechnikov North-Western state medical university. Address: 190068, St.Petersburg, 30 Bolshaya Podjyacheskaya Str.
    Mariya M. Musiichuk, rheumatologist of Federal state budgetary institution Clinical hospital of rheumatology №25. Address: 190068, St.Petersburg, 30 Bolshaya Podjyacheskaya Str.
    Oksana V. Inamova, PhD, chief doctor of Federal state budgetary institution Clinical hospital of rheumatology №25. Address: 190068, St.Petersburg, 30 Bolshaya Podjyacheskaya Str.
    Vadim I. Mazurov, MD, professor, academician of RAS, head of the Department of therapy and Rheumatology named after Ae.Ae. Aeikhvald of Federal state budgetary institution of higher education I.I. Mechnikov North-Western state medical university, honoured worker of science. Address: 191015, St.Petersburg, 41 Kirochnaya Str.

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