Comparative efcacy and safety of urate-lowering therapy for the treatment of hyperuricemia
Abstract
The prevalence of hyperuricemia and gout is increasing, but comparative efficacy and safety of various treatment methods have not yet been evaluated. The network meta-analysis was aimed at comparing the efficacy and safety of various treatments for hyperuricemia. The systemic review included 15 randomized controlled trials (RCTs) involving 7246 patients during the period until January 2016 aimed at comparing the efficacy of various drugs that lower the level of uric acid (UA) (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) in hyperuricemia. The efficacy and safety of drugs (as the outcomes of this analysis) were evaluated after reaching the target level of UA in the serum and the occurrence of adverse events (AEs) regardless of their presence. Efficacy (its values expressed as odds ratios (OR) and 95% confidence intervals (CIs)), and drug safety were assessed by cumulative gradation probabilities. The results show that febuxostat, benzbromarone, probenecid, pegloticase and allopurinol were very effective for the treatment of hyperuricemia compared with placebo. Febuxostat was more effective and safer than other drugs. In addition, febuxostat 120 mg QD was more effective in lowering urate levels (OR: 0.17, 95% CI: 0.120.24) and safer (OR: 0.72, 95% CI: 0.56-0.91) than allopurinol.
References
1. Becker MA et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med, 2005, 353: 2450–2461.
2. Smith E et al. The global burden of gout: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis, 2014, 73: 1470–1476.
3. Roddy E, Choi HK. Epidemiology of gout. Rheum Dis Clin North Am, 2014, 40: 155–175.
4. Conen D et al. Prevalence of hyperuricemia and relation of serum uric acid with cardiovascular risk factors in a developing country. BMC Public Health, 2004, 4(9).
5. Qiu L et al. Prevalence of hyperuricemia and its related risk factors in healthy adults from Northern and Northeastern Chinese provinces. BMC Public Health, 2013, 13(664).
6. AstraZeneca announces top-line results from the Phase III programme of lesinurad in combination with xanthine oxidase inhibitors in gout patients. Available at: https://www.astrazeneca.com/our-company/media-centre/pressreleases/2014/astrazeneca-lesinurad-xanthineoxidase-results-gout-patients-13082014.html (Accessed: 15th February 2016) (2014).
7. Pittman JR, Bross MH. Diagnosis and management of gout. Am Fam Physician, 1999, 59: 1799–1806, 1810.
8. Lin KC, Lin HY, Chou P. Te interaction between uric acid level and other risk factors on the development of gout among asymptomatic hyperuricemic men in a prospective study. J Rheumatol, 2000, 27: 1501–1505.
9. Retrospective analysis of a large cohort. Clin Rheumatol, 2014, 33: 549–553.
10. Luk AJ, Simkin PA. Epidemiology of hyperuricemia and gout. Am J Manag Care, 11: S435–S442, quiz S465-438.
11. Neogi T. Clinical practice. Gout. N Engl J Med, 2011, 364: 443–452.
12. Roddy E, Mallen CD, Doherty M. Gout. BMJ, 2013, 347.
13. Johnson R J, Kivlighn S D, Kim Y G, Suga S, Fogo AB. Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease. Am J Kidney Dis, 1999, 33: 225–234.
14. Edwards NL. Te role of hyperuricemia and gout in kidney and cardiovascular disease. Cleve Clin J Med, 2008, 75 Suppl 5: 13–16.
15. Stamp LK, Chapman PT. Urate-lowering therapy: current options and future prospects for elderly patients with gout. Drugs Aging, 2014, 31: 777–786.
16. Khanna D et al. American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res, 2012, 64: 1431–1446.
17. Jansen TL, Reinders MK, van Roon EN, Brouwers JR. Benzbromarone withdrawn from the European market: another case of “absence of evidence is evidence of absence”? Clin Exp Rheumatol, 2004, 22: 651.
18. Lee MH, Graham GG, Williams KM, Day RO. A beneft-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients? Drug Saf, 2008, 31: 643–665.
19. Ramasamy SN et al. Allopurinol hypersensitivity: a systematic review of all published cases, 1950-2012. Drug Saf, 2013, 36: 953–980.
20. Wu XW, Muzny DM, Lee CC, Caskey C T. Two independent mutational events in the loss of urate oxidase during hominoid evolution. J Mol Evol, 1992, 34: 78–84.
21. Diaz-Torne C, Perez-Herrero N, Perez-Ruiz F. New medications in development for the treatment of hyperuricemia of gout. Curr Opin Rheumatol, 2015, 27: 164–169.
22. Sivera F et al. Multinational evidence-based recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative. Ann Rheum Dis, 2014, 73: 328–335.
23. Ye P et al. Efcacy and tolerability of febuxostat in hyperuricemic patients with or without gout: a systematic review and meta-analysis. Clin Ter, 2013, 35: 180–189.
24. Faruque LI et al. A systematic review and metaanalysis on the safety and efcacy of febuxostat versus allopurinol in chronic gout. Semin Arthritis Rheum, 2013, 43: 367–375.
25. Bucher HC, Guyatt GH, Grifth LE, Walter SD. Te results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol, 1997, 50: 683–691.
26. Caldwell DM, Ades AE Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ, 2005, 331: 897–900.
27. Chen X, Liu MX, Yan GY. Drug-target interaction prediction by random walk on the heterogeneous network. Mol Biosyst, 2012, 8: 1970–1978.
28. Chen X et al. Drug-target interaction prediction: databases, web servers and computational models. Brief Bioinform, 2016, 17: 696–712.
29. Chen X et al. NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning. PLoS Comput Biol, 2016, 12: e1004975.
30. Wang E et al. Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data. Semin Cancer Biol, 2015, 30: 4–12.
31. Lumley T. Network meta-analysis for indirect treatment comparisons. Stat Med, 2002, 21: 2313–2324.
32. Hutton B et al. Te PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and ExplanationsPRISMA Extension for Network Metaanalysis. Ann Intern Med, 2015, 162: 777–784.
33. O’Connor D, Green S, Higgins JP. In Cochrane Hand book for Systematic Reviews of Interventions: Cochrane Book Series (eds Higgins, J. P. & Green, S.), 2008, Ch. 5: 81–94 (John Wiley & Sons, Ltd).
34. Becker MA et al. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twentyeight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efcacy in patients with gout. Arthritis Rheum, 2005, 52: 916–923.
35. Becker MA et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ter, 2010, 12: R63.
36. Huang X et al. An allopurinol-controlled, multicenter, randomized, double-blind, parallel between-group, comparative study of febuxostat in Chinese patients with gout and hyperuricemia. Int J Rheum Dis, 2014, 17: 679–686.
37. Kamatani N et al. An allopurinol-controlled, multicenter, randomized, open-label, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 2 exploratory clinical study. J Clin Rheumatol, 2011, 17: 44–49
38. Kamatani N et al. An allopurinol-controlled, randomized, double-dummy, double-blind, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study. J Clin Rheumatol, 2011, 17: 13–18.
39. Kamatani N et al. Placebo-controlled doubleblind dose-response study of the non-purineselective 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: 35–43.
40. Kamatani N. et al. Placebo-controlled, doubleblind study of the non-purine-selective xanthine oxidase inhibitor Febuxostat (TMX-67) in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study. J Clin Rheumatol, 2011, 17: 19–26.
41. Perez-Ruiz F et al. Treatment of chronic gout in patients with renal function impairment: an open, randomized, actively controlled study. J Clin Rheumatol, 1999, 5: 49–55.
42. Reinders MK et al. Efcacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid afer failure of allopurinol. Ann Rheum Dis, 2009, 68: 51–56.
43. Reinders MK et al. A randomised controlled trial on the efcacy and tolerability with dose escalation of allopurinol 300–600 mg/ day versus benzbromarone 100–200 mg/day in patients with gout. Ann Rheum Dis, 2009, 68: 892–897.
44. Schumacher HR et al. Efects 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. Arthritis Rheum, 2008, 59: 1540–1548.
45. Sundy JS et al. Efcacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA, 2011, 306: 711–720.
46. Xu S. et al. A phase 3, multicenter, randomized, allopurinol-controlled study assessing the safety and efcacy of oral febuxostat in Chinese gout patients with hyperuricemia. Int J Rheum Dis, 2015, 18: 669–678.
47. Yu KH et al. Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: a randomized, open-label, multicentre, allopurinol-controlled study. Scand J Rheumatol, 2016, 45: 304–311.
48. Higgins JP, Altman DG. In Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series (eds Higgins, J. P. & Green, S.), 2008, Ch. 8: 187–241 (John Wiley & Sons, Ltd).
49. Higgins JP, Tompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ, 2003, 327: 557–560.
50. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment metaanalysis: an overview and tutorial. J Clin Epidemiol, 2011, 64: 163–171.
51. Li T, Puhan MA, Vedula SS, Singh S, Dickersin K. Network meta-analysis-highly attractive but more methodological research is needed. BMC Med., 2011, 9: 79.
52. Jansen JP et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1. Value Health, 2011, 14: 417–428.
53. Jansen JP, Naci H. Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of efect modifers. BMC Med., 2013, 11: 159.
54. Ko TM et al. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ, 2015, 351: h4848.
55. Beard SM, von Scheele BG, Nuki G, Pearson IV. Cost-efectiveness of febuxostat in chronic gout. Eur J Health Econ., 2014, 15: 453–463.
56. Tayar JH, Lopez-Olivo MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database Syst Rev., 2013, 11: 202–203.
57. Zhang W 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 Terapeutics (ESCISIT). Ann Rheum Dis., 2006, 65: 1312–1324.
Review
For citations:
Comparative efcacy and safety of urate-lowering therapy for the treatment of hyperuricemia. Meditsinskiy sovet = Medical Council. 2018;(9):68-81. (In Russ.)
Views:
3662
Email this article 