Adherence to urate-lowering therapy while following the national guidelines for the management of patients with gout (preliminary evidence)

Low compliance in patients with gout is one of the reasons for inadequate disease control.

Objective: to study treatment adherence in compliance with the national guidelines for the management of gout patients, which provide for the continuous use of urate-lowering drugs, a gradual increase in their dose until the target serum uric acid (UA) level is reached, prophylactic antiinflammatory therapy, and regular patient monitoring.

Patients and methods. This was a prospective single-center study. By now, 60 of the 80 enrolled gout patients had completed the study. The follow-up period was at least 24 weeks, during which allopurinol or febuxostat was used at the final dose.
During initiation of urate-lowering therapy, allopurinol 100 mg/day was prescribed, followed by dose titration to reach the target UA level (<360 μmol/L) for all patients or <300 μmol/L for those with severe tophaceous gout.
Patients with ineffective allopurinol and/or in the presence of its associated adverse reactions were prescribed febuxostat (Azurix®) 80 mg/day; the dose was increased up to 120 mg/day as needed.
To prevent acute arthritis attacks, all the patients received a nonsteroidal anti-inflammatory drug (NSAID) at minimal therapeutic doses or colchicine 0.5 mg/day, and in the presence of contraindications to their use, they took glucocorticoid (GC) 7.5 mg/day calculated with reference to prednisolone.
The four-item Morisky–Green questionnaire was used to assess patient adherence to therapy.

Results and discussion. At 24 weeks after the start of their follow-up, 53 (88%) of the 60 patients received urate-lowering therapy; 38 (72%) of these 53 patients achieved the target UA level.
The dose of allopurinol was titrated in 19 patients; and 10 (53%) of them achieved the target serum UA levels.
Due to its inefficacy, allopurinol was replaced by febuxostat in 24 patients. In this group, the target UA level was recorded in 16 (67%) patients.
Seventeen patients were immediately prescribed febuxostat that could achieve the target UA level in 12 (71%) of them.
All the patients enrolled in the study received prophylactic anti-inflammatory therapy: NSAIDs were used in 9 (15%) patients, colchicine and GC were given to 46 (77%) and 5 (8%), respectively.
Twenty-six (49%) patients who had completed the investigation were ascertained to have a high adherence therapy. Moderate and low adherence was observed in 9 (17%) and 18 (34%) patients, respectively. High therapy adherence was noted in more than half of cases in the febuxostat group and in 40% in the allopurinol one.

Conclusion. High compliance in gout patients can be achieved through the observance of the national guidelines for the treatment of this disease.

1. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-8. Arthritis Rheum. 2011 Oct;63(10):3136-41. doi: 10.1002/art.30520.

2. Kuo CF, Grainge MJ, Zhang W, et al. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol. 2015 Nov;11(11):649-62. doi: 10.1038/nrrheum.2015.91. Epub 2015 Jul 7.

3. Mikuls TR, Saag KG. New insights into gout epidemiology. Curr Opin Rheumatol. 2006 Mar;18(2):199-203. doi: 10.1097/01.bor.0000209435.89720.7c.

4. Weaver AL, Cheh MA, Kennison RH. How PCP education can impact gout management: the gout essentials. J Clin Rheumatol. 2008 Oct;14(5 Suppl):S42-6. doi: 10.1097/RHU.0b013e3181896b1e.

5. Keenan RT, Lehman RA, O'Brien WR, et al. Gout management in primary care vs. rheumatology: evidence for suboptimal treatment [abstract]. Arthritis Rheum. 2009; 60(10):1110.

6. Juraschek SP, Kovell LC, Miller ER, et al. Gout, urate-lowering therapy, and uric acid levels among adults in the United States. Arthritis Care Res (Hoboken). 2015 Apr;67(4): 588-92. doi: 10.1002/acr.22469.

7. Kuo CF, Grainge MJ, Mallen C, et al. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis. 2015 Apr; 74(4):661-7. doi: 10.1136/annrheumdis2013-204463. Epub 2014 Jan 15.

8. Cottrell E, Crabtree V, Edwards JJ, et al. Improvement in the management of gout is vital and overdue: an audit from a UK primary care medical practice. BMC Fam Pract. 2013 Nov 14;14:170. doi: 10.1186/1471-2296-14-170.

9. Kuo CF, Grainge MJ, Mallen C, et al. Eligibility for and prescription of urate-lowering treatment in patients with incident gout in England. JAMA. 2014 Dec 24-31;312(24): 2684-6. doi: 10.1001/jama.2014.14484.

10. https://public.tableau.com/profile/hqi2803#!/vizhome/Goutsinglemap/AtlasofHealthcareVariationGout. 2018 7 May 2020.

11. Doherty M, Jansen TL, Nuki G, et al. Gout: why is this curable disease so seldom cured? Ann Rheum Dis. 2012 Nov;71(11): 1765-70. doi: 10.1136/annrheumdis-2012-201687. Epub 2012 Aug 3.

12. Sarawate CA, Patel PA, Schumacher HR, et al. Serum urate levels and gout flares: Analysis from managed care data. J Clin Rheumatol. 2006 Apr;12(2):61-5. doi: 10.1097/01.rhu.0000209882.50228.9f.

13. Dehlin M, Ekström EH, Petzold M, et al. Factors associated with initiation and persistence of urate-lowering therapy. Arthritis Res Ther. 2017 Jan 17;19(1):6. doi: 10.1186/s13075-016-1211-y.

14. Tausche AK, Reuss-Borst M, Koch U. Urate lowering therapy with febuxostat in daily practice-a multicentre, open-label, prospective observational study. Int J Rheumatol. 2014;2014:123105. doi: 10.1155/2014/123105. Epub 2014 Sep 3.

15. http://cr.rosminzdrav.ru/#!/recomend/174.

16. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017 Jan;76(1):29-42. doi: 10.1136/annrheumdis-2016-209707. Epub 2016 Jul 25.

17. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020 Jun;72(6): 744-60. doi: 10.1002/acr.24180. Epub 2020 May 11.

18. Abhishek A, Doherty M. Education and non-pharmacological approaches for gout. Rheumatology (Oxford). 2018 Jan 1; 57(suppl_1):i51-i58. doi: 10.1093/rheumatology/kex421.

19. Eliseev MS, Chikina MN. A single-center open prospective study of the effect of combined urate-lowering and anti-inflammatory therapy on the course of gout. Russkii meditsinskii zhurnal. 2019;11(II):90-5. (In Russ.).

20. https://grls.rosminzdrav.ru/grls.aspx?s=фебуксостат&m=mnn

21. https://grls.rosminzdrav.ru/grls.aspx?s=аллопуринол&m=mnn

22. Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a selfreported measure of medication adherence. Med Care. 1986 Jan;24(1):67-74. doi: 10.1097/00005650-198601000-00007.

23. Bardin T, Richette P. Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options. BMC Med. 2017 Jul 3;15(1):123. doi: 10.1186/s12916-017-0890-9.

24. Mantarro S, Capogrosso-Sansone A, Tuccori M, et al. Allopurinol adherence among patients with gout: an Italian general practice database study. Int J Clin Pract. 2015 Jul;69(7):757-65. doi: 10.1111/ijcp.12604. Epub 2015 Feb 16.

25. Huang X, Du H, Gu J, 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 Jul;17(6):679-86. doi: 10.1111/1756-185X.12266.

26. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005 Dec 8; 353(23):2450-61. doi: 10.1056/NEJMoa050373.

27. Becker MA, Schumacher HR, Espinoza LR, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther. 2010;12(2): R63. doi: 10.1186/ar2978. Epub 2010 Apr 6.

28. Gill I, Dalbeth N, 'Ofanoa M, Goodyear-Smith F. Interventions to improve uptake of urate-lowering therapy in patients with gout: a systematic review. BJGP Open. 2020 Aug 25;4(3):bjgpopen20X101051. doi: 10.3399/bjgpopen20X101051.Print 2020 Aug.

29. Eliseev M, Zhelyabina O, Chikina M, Vladimirov S. Assessment of therapy adherence and treatment results in gout patients who attended schools for patients and in those who did not. Ann Rheum Dis. 2018;77 Suppl:A654.