Realities of modern urate-reducing therapy for gout

Introduction. In the treatment of a patient with gout, it is important to achieve the target level of uric acid (UA) < 360 μmol/l, which reduces the frequency of acute attacks of arthritis and improves the prognosis of comorbid diseases. Relief of acute gouty arthritis causes much less difficulty compared with the appointment of urate-l owering therapy (UST). The reasons for not achieving the target level of MC can be both objective and subjective.

Aim. To analyze the objective and subjective components of the activity and effectiveness of UST in real outpatient practice.

Material and methods. A cross- sectional study of 117 randomly selected outpatient records of patients diagnosed with gout. Mean age 58.6 ± 13.1, mean UA level 423.7 ± 122.4 μmol/L. Additionally, an anonymous survey of doctors and patients with gout was conducted on the issues of UST.

Results. Patients with gout in the analyzed group were characterized by a high degree of polymorbidity: women and men, respectively, had arterial hypertension in 100 and 79%, type 2 diabetes mellitus in 39 and 23%, osteoarthritis in 73 and 57%. With inevitable polypharmacy, UST was prescribed in 37.6% of patients. Achievement of target levels of UA was registered in 23.8% of men and 39.4% of women. Failure to achieve the target sUA was associated with diuretics, elevated creatinine, and body mass index. Physicians were more than 70% active in prescribing UST, but knowledge of a single target UA level was demonstrated by 6 to 13%, depending on work experience, with an excessive assumption of UST use during an acute gout attack (19 to 36.5%). 

Conclusion. All components of the diagnostic and therapeutic process of curing a gouty patient need to be improved.

1. Elfishawi M.M., Zleik N., Kvrgic Z., Michet C.J. Jr, Crowson C.S., Matteson E.L., Bongartz T. The Rising Incidence of Gout and the Increasing Burden of Comorbidities: A Population- based Study over 20 Years. J Rheumatol. 2018;45(4):574–579. https://doi.org/10.3899/jrheum.170806.

2. Safiri S., Kolahi A.A., Cross M., Carson- Chahhoud K., Hoy D., Almasi- Hashiani A. et al. Prevalence, Incidence, and Years Lived With Disability Due to Gout and Its Attributable Risk Factors for 195 Countries and Territories 1990–2017: A Systematic Analysis of the Global Burden of Disease Study 2017. Arthritis Rheumatol. 2020;72(11):1916–1927. https://doi.org/10.1002/art.41404.

3. Galushko E.A., Nasonov E.L. Prevalence of rheumatic diseases in Russia. Almanac of Clinical Medicine. 2018;46(1):32–39. (In Russ.) https://doi.org/10.18786/2072-0505-2018-46-1-32-39.

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):3136–3141. https://doi.org/10.1002/art.30520.

5. Taskina E.A., Alekseeva L.I., Kashevarova N.G., Panevin T.S., Lila A.M. Osteoarthritis and hyperuricemia: is there a relationship? Doctor.Ru. 2021;20(7):26–31. (In Russ.) https://doi.org/10.31550/1727-2378-2021-207-26-31.

6. Gao C., Chen Z., Ma J., Xie J., Zhang W., Ren H., Chen X. Prevalence of and risk factors for high-altitude hyperuricaemia in Bai individuals: a cross- sectional study. J Int Med Res. 2021;49(7):3000605211028140. https://doi.org/10.1177/03000605211028140.

7. Shalnova S.A., Deev A.D., Artamonov G.V., Duplyakov D.V., Efanov A.Yu., Zhernakova Yu.V. et al. Hyperuricemia and its correlates in the Russian population (results of Esse- RF epidemiological study). Rational Pharmacotherapy in Cardiology. 2014;10(2):153–159. (In Russ.) https://doi.org/10.20996/1819-6446-2014-10-2-153-159.

8. Bardin T., Richette P. Definition of hyperuricemia and gouty conditions. Curr Opin Rheumatol. 2014;26(2):186–191. https://doi.org/10.1097/BOR.0000000000000028.

9. Martillo M.A., Nazzal L., Crittenden D.B. The crystallization of monosodium urate. Curr Rheumatol Rep. 2014;16(2):400. https://doi.org/10.1007/s11926013-0400-9.

10. Lin K.C., Lin H.Y., Chou P. The 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(6):1501–1505. Available at: https://pubmed.ncbi.nlm.nih.gov/10852278/.

11. Saag K.G., Choi H. Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis Res Ther. 2006;8(Suppl. 1):S2. https://doi.org/10.1186/ar1907.

12. Dalbeth N., House M.E., Aati O., Tan P., Franklin C., Horne A. et al. Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout: a dual energy CT study. Ann Rheum Dis. 2015;74(5):908–911. https://doi.org/10.1136/annrheumdis-2014-206397.

13. Park J.J., Roudier M.P., Soman D., Mokadam N.A., Simkin P.A. Prevalence of birefringent crystals in cardiac and prostatic tissues, an observational study. BMJ Open. 2014;4(7):e005308. https://doi.org/10.1136/bmjopen-2014-005308.

14. Dolgova L.N., Krasivina I.G., Dolgov N.V., Lugovkina D.G. Metabolic risks of hyperuricemia. Meditsinskiy Sovet. 2019;(18):76–84. (In Russ.) https://doi.org/10.21518/2079-701X-2019-18-76-84.

15. Chazova I.E., Zhernakova Yu.V., Kislyak O.A., Nedogoda S.V., Podzolkov V.I., Oshchepkova E.V. et al. Consensus on patients with hyperuricemia and high cardiovascular risk treatment. Systemic Hypertension. 2019;16(4): 8–21. (In Russ.) Available at: https://www.syst-hypertension.ru/jour/article/view/593.

16. Lopez- Pineda A., Cordero A., Carratala-Munuera C., Orozco-Beltran D., Quesada J.A., Bertomeu-Gonzalez V. et al. Hyperuricemia as a prognostic factor after acute coronary syndrome. Atherosclerosis. 2018;269:229–235. https://doi.org/10.1016/j.atherosclerosis.2018.01.017.

17. Wheeler J.G., Juzwishin K.D., Eiriksdottir G., Gudnason V., Danesh J. Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls: prospective study and meta-analysis. PLoS Med. 2005;2(3):e76. https://doi.org/10.1371/journal.pmed.0020076.

18. Topolyanskaya S.V. Hyperuricemia and cardiovascular diseases. Therapy. 2020;(7):71–82. (In Russ.) https://doi.org/10.18565/therapy.2020.7.71-82.

19. Xiao L., Lin S., Zhan F. The association between serum uric acid level and changes of MRI findings in knee osteoarthritis: A retrospective study (A STROBE-compliant article). Medicine (Baltimore). 2019;98(21):e15819. https://doi.org/10.1097/MD.0000000000015819.

20. Lee K.W., Shin D. Concurrent presence of high serum uric acid and inflammation is associated with increased incidence of type 2 diabetes mellitus in Korean adult population. Sci Rep. 2022;12(1):11000. https://doi.org/10.1038/s41598-022-15176-9.

21. Joo K., Kwon S.R., Lim M.J., Jung K.H., Joo H., Park W. Prevention of comorbidity and acute attack of gout by uric acid lowering therapy. J Korean Med Sci. 2014;29(5):657–661. https://doi.org/10.3346/jkms.2014.29.5.657.

22. Nasonova V.A., Barskova V.G. Early diagnostic and treatment of gout – is scientifically based reguirements for improvement of labour and living prognosis of patients. Rheumatology Science and Practice. 2004;42(1):5–7. (In Russ.) Available at: https://rsp.mediar-press.net/rsp/article/view/1227/898.

23. Solomon D.H., Bates D.W., Panush R.S., Katz J.N. Costs, outcomes, and patient satisfaction by provider type for patients with rheumatic and musculoskeletal conditions: a critical review of the literature and proposed methodologic standards. Ann Intern Med. 1997;127(1):52–60. https://doi.org/10.7326/0003-4819-127-1-199707010-00009.

24. Begun D.N. Problems of the organization of the medical care by the patient with rheumatic diseases in Russia. Review of literature. Modern Problems of Science and Education. 2015;(5):105. (In Russ.) Available at: https://science-education.ru/ru/article/view?id=21855.

25. Gamez- Nava J.I., Gonzalez- Lopez L., Davis P., Suarez- Almazor M.E. Referral and diagnosis of common rheumatic diseases by primary care physicians. Br J Rheumatol. 1998;37(11):1215–1219. https://doi.org/10.1093/rheumatology/37.11.1215.

26. Kumar K., Daley E., Carruthers D.M., Situnayake D., Gordon C., Grindulis K. et al. Delay in presentation to primary care physicians is the main reason why patients with rheumatoid arthritis are seen late by rheumatologists. Rheumatology (Oxford). 2007;46(9):1438–1440. https://doi.org/10.1093/rheumatology/kem130.

27. Roddy E., Mallen C.D., Hider S.L., Jordan K.P. Prescription and comorbidity screening following consultation for acute gout in primary care. Rheumatology (Oxford). 2010;49(1):105–111. https://doi.org/10.1093/rheumatology/kep332.

28. Насонов Е.Л. (ред.). Российские клинические рекомендации. Ревматология. М.: ГЭОТАР-Медиа; 2017. 464 с. Nasonov E.L. (ed.). Russian clinical guidelines. Rheumatology. Moscow: GEOTAR-Media; 2017. 464 p. (In Russ.)

29. Brucato A., Cianci F., Carnovale C. Management of hyperuricemia in asymptomatic patients: A critical appraisal. Eur J Intern Med. 2020;74:8–17. https://doi.org/10.1016/j.ejim.2020.01.001.

30. Chazova I.E., Zhernakova Yu.V. Diagnosis and treatment of arterial hypertension (Guidelines). Systemic Hypertension. 2019;16(1):6–31. (In Russ.) Available at: https://www.syst-hypertension.ru/jour/article/view/576.

31. Richette P., Doherty M., Pascual E., Barskova V., Becce F., Castañeda- Sanabria J. et al. 2016 updated EULAR evidence- based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29–42. https://doi.org/10.1136/annrheumdis-2016-209707.

32. Richette P., Doherty M., Pascual E., Barskova V., Becce F., Castaneda J. et al. 2018 updated European League Against Rheumatism evidence-b ased re commendations for the diagnosis of gout. Ann Rheum Dis. 2020;79(1): 31–38. https://doi.org/10.1136/annrheumdis-2019-215315.

33. Mazurov V.I., Belyayeva I.B., Petrova M.S., Bashkinov R.A. Pathogenetic therapy of gout in comorbid patients: the advantage of febuxostat. Effective Pharmacotherapy. 2022;18(38):16–22. (In Russ.) Available at: https://umedp.ru/articles/patogeneticheskaya_terapiya_podagry_u_komorbidnykh_patsientov_preimushchestvo_febuksostata_.html.

34. Eliseev M.S., Eliseeva M.E. Modern Aspects of Pathogenesis and Correction of Hyperuricemia and Associated Conditions. Effective Pharmacotherapy. 2019;15(8):32–40. (In Russ.) Available at: https://umedp.ru/articles/sovremennye_aspekty_patogeneza_i_korrektsii_giperurikemii_a_takzhe_assotsiirovannykh_s_ney_sostoyani.html.

35. Perez- Ruiz F., Moreno- Lledó A., Urionagüena I., Dickson A.J. Treat to target in gout. Rheumatology (Oxford). 2018;57(Suppl. 1):i20–i26. https://doi.org/10.1093/rheumatology/kex442.

36. Eliseev M.S., Chikina M.N., Zhelyabina O.V. Open 6-month study on the efficacy of dose titration of allopurinol in patients with gout as part of the “treat to target” strategy. RMJ. 2022;(6):17–22. (In Russ.) Available at: https://www.rmj.ru/articles/revmatologiya/Otkrytoe_6-mesyachnoe_issledovanie_effektivnosti_titrovaniya_dozy_allopurinola_u_pacientov_s_podagroy_v_ramkah_strategii_lechenie_do_celi/.

37. Jennings C.G., Mackenzie I.S., Flynn R., Ford I., Nuki G., De Caterina R. et al. Up-titration of allopurinol in patients with gout. Semin Arthritis Rheum. 2014;44(1):25–30. https://doi.org/10.1016/j.semarthrit.2014.01.004.

38. Becker M.A., Fitz- Patrick D., Choi H.K., Dalbeth N., Storgard C., Cravets M., Baumgartner S. An open-label, 6-month study of allopurinol safety in gout: The LASSO study. Semin Arthritis Rheum. 2015;45(2):174–183. https://doi.org/10.1016/j.semarthrit.2015.05.005.

39. Frampton J.E. Febuxostat: a review of its use in the treatment of hyperuricaemia in patients with gout. Drugs. 2015;75(4):427–438. https://doi.org/10.1007/s40265-015-0360-7.

40. Petrova M.S., Mazurov V.I., Inamova O.V. Febuxostat for treatment of chronic hyperuricemia in gout patients. Meditsinskiy Sovet. 2017;(17):114–122. (In Russ.) https://doi.org/10.21518/2079701X-2017-17-114-122.

41. Perez- Ruiz F., Punzi L. Hyperuricemia and tissue monourate deposits: prospective therapeutic considerations. Eur Rev Med Pharmacol Sci. 2015;19(9):1549–1552. Available at: https://www.europeanreview.org/article/8869.

42. Yamanaka H. Japanese guideline for the management of hyperuricemia and gout: second edition. Nucleosides Nucleotides Nucleic Acids. 2011;30(12):1018–1029. https://doi.org/10.1080/15257770.2011.596496.

43. White W.B., Saag K.G., Becker M.A., Borer J.S., Gorelick P.B., Whelton A. et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med. 2018;378(13):1200–1210. https://doi.org/10.1056/NEJMoa1710895.

44. Gao L., Wang B., Pan Y., Lu Y., Cheng R. Cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout: A systematic and meta-analysis. Clin Cardiol. 2021;44(7):907–916. https://doi.org/10.1002/clc.23643.

45. Mackenzie I.S., Ford I., Nuki G., Hallas J., Hawkey C.J., Webster J. et al. Longterm cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial. Lancet. 2020;396(10264):1745–1757. https://doi.org/10.1016/S0140-6736(20)32234-0.

46. Suzuki S., Yoshihisa A., Yokokawa T., Kobayashi A., Yamaki T., Kunii H. et al. Comparison between febuxostat and allopurinol uric acid-lowering therapy in patients with chronic heart failure and hyperuricemia: a multicenter randomized controlled trial. J Int Med Res. 2021;49(12): 3000605211062770. https://doi.org/10.1177/03000605211062770 .

47. Harrold L.R., Mazor K.M., Negron A., Ogarek J., Firneno C., Yood R.A. Primary care providers’ knowledge, beliefs and treatment practices for gout: results of a physician questionnaire. Rheumatology (Oxford). 2013;52(9):1623–1629. https://doi.org/10.1093/rheumatology/ket158.