Febuxostat efficacy in patients with gout depending on kidney function
DOI: 10.32364/2587-6821-2022-6-3-140-147
Aim: to determine the probability of achieving the target serum uric acid (UA) level during therapy with febuxostat (in the tablet form) in patients with gout stratified depending on kidney function, including patients with type 2 diabetes mellitus (DM2).
Patients and Methods: the study included patients over 18 years of age with gout who had not previously taken febuxostat or other urate-lowering drugs for at least 2 weeks before inclusion, with a serum UA level >360 µmoL/L. All were prescribed with febuxostat in the tablet form 80 mg/day. If the target serum UA level was not reached (<360 µmoL/L), the dosage level was increased up to 120 mg/day. Laboratory tests included the determination of blood glucose, creatinine, UA. Initially, patients were divided into groups according to chronic kidney disease (CKD) stages by the level of estimated glomerular filtration rate (eGFR) by CKD-EPI: C1 — high or optimal renal function (>90 mL/min/1.73 m2), C2 — slightly reduced renal function (60–89 mL/min/1.73 m2), C3 — moderately/considerably reduced renal function (30–59 mL/min/1.73 m2), C4 — significantly reduced renal function (15–29 mL/min/1.73 m2). Patients with DM2 were analyzed separately. The follow-up period covered at least 26 weeks: the primary endpoint was to achieve the target serum UA level, and the eGFR tendency was also evaluated.
Results: 136 patients with gout were examined. DM2 was in 38 (27.9%) patients. CKD C0–1 was detected in 30 (22.1%) patients, C2 — in 28 (20.6%), C3 — in 62 (45.6%), C4 — in 16 (11.8%). Febuxostat (in the tablet form) was received at a dose of 80 mg/day in 98 (72.1%) patients, 120 mg/day in 38 (27.9%) patients. There was the following preventive administration of anti-inflammatory therapy: colchicine — 59 (43.4%) patients, NSAIDs — 51 (37.5%) patients, glucocorticosteroids — 12 (8.8%) patients, no drug therapy — 14 (10.3%) patients. UA level significantly decreased in all groups, the average value of Δ MK and the frequency of achieving the target serum UA level were comparable. Achievement of the target serum UA level in general was in 84% of patients; in C0–1, C2, C3, C4 — in 83, 89, 82 and 81% of patients, respectively. The mean eGFR values relative to the baseline increased by the end of the study in all groups, but significant differences were only in patients with C0–1: 101.3±18.1 mL/min/1.73 m2 vs 102.8±28.6 mL/min/1.73 m2 (p=0.002). Of the 38 patients with DM2, 33 (87%) achieved the target serum UA level. In 2 patients with CKD C3, ALT and AST increased up to two norms (when taking febuxostat 120 mg/day).
Conclusion: the possibility of achieving the target serum UA level when taking febuxostat (in the tablet form) in patients with gout does not depend on kidney function, including in patients with DM2.
Keywords: gout, febuxostat, glomerular filtration rate, chronic kidney disease, diabetes mellitus.
For citation: Eliseev M.S., Zhelyabina O.V., Chikina M.N., Thakokov M.M. Febuxostat efficacy in patients with gout depending on kidney function. Russian Medical Inquiry. 2022;6(3):140–147 (in Russ.). DOI: 10.32364/2587-6821-2022-6-3-140-147.
About the authors:
Maxim S. Eliseev — C. Sc. (Med.), Head of the Laboratory of Microcrystalline Arthritis, Research Institute of Rheumatology named after V.A. Nasonova; 34A, Kashirskoe road, Moscow, 115522, Russian Federation; ORCID iD 0000-0003-1191-5831.
Olga V. Zhelyabina — Junior Researcher at the Laboratory of Microcrystalline Arthritis, Research Institute of Rheumatology named after V.A. Nasonova; 34A, Kashirskoe road, Moscow, 115522, Russian Federation; ORCID iD 0000-0002-5394-7869.
Maria N. Chikina — Junior Researcher at the Laboratory of Microcrystalline Arthritis, Research Institute of Rheumatology named after V.A. Nasonova; 34A, Kashirskoe road, Moscow, 115522, Russian Federation; ORCID iD 0000-0002-8777-7597.
Muradin M. Thakokov — C. Sc. (Med.), oncologist; Vidnovskaya Regional Clinical Hospital; 15, Zavodskaya str., Vidnoye, 142700, Russian Federation; ORCID iD 0000-0002-4504-4977.
Contact information: Maxim S. Eliseev, e-mail: elicmax@yandex.ru.
Funding source: the work was carried out within the framework of the scientific study "Optimization of methods concerning symptomatic anti-inflammatory therapy in patients with microcrystalline arthritis (gout, calcium pyrophosphate dihydrate crystal deposition disease)" (No. 2020-397-007).
Financial Disclosure: the author has no financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 22.12.2021.
Revised 21.01.2022.
Accepted 15.02.2022.
2. Uchida S., Kumagai T., Chang W.X. et al. Time to Target Uric Acid to Retard Chronic Kidney Disease Progression. Contrib Nephrol. 2018;192:56–68. DOI: 10.1159/000484279.
3. Елисеев М.С. Хроническая болезнь почек: роль гиперурикемии и возможности уратснижающей терапии. Современная ревматология. 2018;12(1):60–65. DOI: 10.14412/1996-7012-2018-1-60-65. [Eliseev M.S. Chronic kidney disease: the role of hyperuricemia and the possibility of urate-lowering therapy. Modern Rheumatology Journal. 2018;12(1):60–65 (in Russ.). DOI: 10.14412/1996-7012-2018-1-60-65].
4. Jaffe D.H., Klein A.B., Benis A. et al. Incident gout and chronic Kidney Disease: healthcare utilization and survival. BMC Rheumatol. 2019;3:11. DOI: 10.1186/s41927-019-0060-0.
5. Чикина М.Н., Елисеев М.С., Желябина О.В. Практическое применение национальных клинических рекомендаций по лечению подагры (предварительные данные). Современная ревматология. 2020;14(2):97–103. DOI: 10.14412/1996-7012-2020-2-97-103. [Chikina M.N., Eliseev M.S., Zhelyabina O.V. Practical application of national clinical guidelines for the management of gout (preliminary data). Modern Rheumatology Journal. 2020;14(2):97–103 (in Russ.). DOI: 10.14412/1996-7012-2020-2-97-103].
6. Чикина М.Н., Желябина О.В., Елисеев М.С. Влияние уратснижающей терапии на показатели качества жизни у пациентов с подагрой. Современная ревматология. 2021;15(3):62–68. DOI: 10.14412/1996-7012-2021-3-62-68. [Chikina M.N., Zhelyabina O.V., Eliseev M.S. Impact of urate-lowering therapy on quality of life indicators in patients with gout. Modern Rheumatology Journal. 2021;15(3):62–68 (in Russ.). DOI: 10.14412/1996-7012-2021-3-62-68].
7. Kumagai T., Ota T., Tamura Y. et al. Time to target uric acid to retard CKD progression. Clin Exp Nephrol. 2017;21(2):182–192. DOI: 10.1007/s10157-016-1288-2.
8. Jeyaruban A., Hoy W., Cameron A. et al. Hyperuricaemia, gout and allopurinol in the CKD Queensland registry. J Nephrol. 2021;34(3):753–762. DOI: 10.1007/s40620-020-00937-4.
9. Yen F.S., Wei J.C., Chang C.L. et al. Urate-lowering Therapy and Chronic Kidney Disease Development in Patients with Gout. Int J Med Sci. 2021;18(12):2599–2606. DOI: 10.7150/ijms.59698.
10. FitzGerald J.D., Dalbeth N., Mikuls T. et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744–60. DOI: 10.1002/acr.24180.
11. Richette P., Doherty M., Pascual E. et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29–42. DOI: 10.1136/annrheumdis-2016-209707.
12. Pascart T., Latourte A., Flipo R.M. et al. 2020 recommendations from the French Society of Rheumatology for the management of gout: Urate-lowering therapy. Joint Bone Spine. 2020;87(5):395–404. DOI: 10.1016/j.jbspin.2020.05.002.
13. Premachandra K.H., Day R.O., Roberts D.M. Managing hyperuricemia and gout in chronic kidney disease: a clinical conundrum. Curr Opin Nephrol Hypertens. 2021;30(2):245–251. DOI: 10.1097/MNH.0000000000000691.
14. Stamp L.K., Farquhar H., Pisaniello H.L. et al. Management of gout in chronic kidney disease: a G-CAN Consensus Statement on the research priorities. Nat Rev Rheumatol. 2021;17(10):633–641. DOI: 10.1038/s41584-021-00657-4.
15. Государственный реестр лекарственных средств. Фебуксостат. (Электронный ресурс.) URL: https://grls.rosminzdrav.ru/grls.aspx?s=фебуксостат&m=mnn (дата обращения: 20.12.2021). [State register of medicines. Febuxostat. (Electronic resource.) URL: https://grls.rosminzdrav.ru/grls.aspx?s=фебуксостат&m=mnn (access date: 20.12.2021) (in Russ.)].
16. Levey A.S., Stevens L.A., Schmid C.H. et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–612. DOI: 10.7326/0003-4819-150-9-200905050-00006.
17. Клинические рекомендации. Хроническая болезнь почек. (Электронный ресурс.) URL: https://rusnephrology.org/wp-content/uploads/2020/12/CKD_final.pdf (дата обращения: 20.12.2021). [Clinical recommendations. Chronic kidney disease. (Electronic resource.) URL: https://rusnephrology.org/wp-content/uploads/2020/12/CKD_final.pdf (access date: 20.12.2021) (in Russ.)].
18. Чикина М.Н., Елисеев М.С., Желябина О.В. Сравнение эффективности и безопасности различных противовоспалительных препаратов при инициации уратснижающей терапии у пациентов с подагрой (предварительные данные). Современная ревматология. 2021;15(2):50–56. DOI: 10.14412/1996-7012-2021-2-50-56. [Chikina M.N., Eliseev M.S., Zhelyabina O.V. Comparison of the efficacy and safety of various anti-inflammatory drugs in urate-lowering therapy initiation in patients with gout (preliminary data). Modern Rheumatology Journal. 2021;15(2):50–56 (in Russ.). DOI: 10.14412/1996-7012-2021-2-50-56].
19. Becker M.A., Schumacher H.R. Jr., Wortmann RL. et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353(23):2450–2461. DOI: 10.1056/NEJMoa050373.
20. Fuldeore M.J., Riedel A.A., Zarotsky V. et al. Chronic kidney disease in gout in a managed care setting. BMC Nephrol. 2011;12:36. DOI: 10.1186/1471-2369-12-36.
21. Kumar S., Gow P. A survey of indications, results and complications of surgery for tophaceous gout. N Z Med J. 2002;115(1158):U109. PMID: 12362184.
22. Schumacher H.R. Jr., 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. Arthritis Rheum. 2008;59(11):1540–1548. DOI: 10.1002/art.24209.
23. Juge P.A., Truchetet M.E., Pillebout E. et al. Efficacy and safety of febuxostat in 73 gouty patients with stage 4/5 chronic kidney disease: A retrospective study of 10 centers. Joint Bone Spine. 2017;84(5):595–598. DOI: 10.1016/j.jbspin.2016.09.020.
24. Yamaguchi A., Harada M., Yamada Y. et al. Identification of chronic kidney disease patient characteristics influencing the renoprotective effects of febuxostat therapy: a retrospective follow-up study. BMC Nephrol. 2017;18(1):162. DOI: 10.1186/s12882-017-0572-z.
25. Shibagaki Y., Ohno I., Hosoya T., Kimura K. Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction. Hypertens Res. 2014;37(10):919–925. DOI: 10.1038/hr.2014.107.
26. Borghi C., Perez-Ruiz F. Urate lowering therapies in the treatment of gout: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2016;20(5):983–992. PMID: 27010159.
27. 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. Arthritis Res Ther. 2010;12(2):R63. DOI: 10.1186/ar2978.
28. Gunawardhana L., Becker M.A., Whelton A. et al. Efficacy and safety of febuxostat extended release and immediate release in patients with gout and moderate renal impairment: phase II placebo-controlled study. Arthritis Res Ther. 2018;20(1):99. DOI: 10.1186/s13075-018-1593-0.
29. Farquhar H., Vargas-Santos A.B., Pisaniello H.L. et al. Efficacy and safety of urate-lowering therapy in people with kidney impairment: a GCAN-initiated literature review. Rheumatol Adv Pract. 2021;5(1):rkaa073. DOI: 10.1093/rap/rkaa073.
30. Peng Y.L., Tain Y.L., Lee C.T. et al. Comparison of uric acid reduction and renal outcomes of febuxostat vs allopurinol in patients with chronic kidney disease. Sci Rep. 2020;10(1):10734. DOI: 10.1038/s41598-020-67026-1.
31. Kimura K., Hosoya T., Uchida S. et al. Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial. Am J Kidney Dis. 2018;72(6):798–810. DOI: 10.1053/j.ajkd.2018.06.028.
32. Kanji T., Gandhi M., Clase C.M., Yang R. Urate lowering therapy to improve renal outcomes in patients with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol. 2015;16:58. DOI: 10.1186/s12882-015-0047-z.
33. Hsu Y.O., Wu I.W., Chang S.H. et al. Comparative Renoprotective Effect of Febuxostat and Allopurinol in Predialysis Stage 5 Chronic Kidney Disease Patients: A Nationwide Database Analysis. Clin Pharmacol Ther. 2020;107(5):1159–1169. DOI: 10.1002/cpt.1697.
34. Tsuruta Y., Mochizuki T., Moriyama T. et al. Switching from allopurinol to febuxostat for the treatment of hyperuricemia and renal function in patients with chronic kidney disease. Clin Rheumatol. 2014;33(11):1643–1648. DOI: 10.1007/s10067-014-2745-5.
35. Chou H.W., Chiu H.T., Tsai C.W. et al. Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study. Nephrol Dial Transplant. 2018;33(9):1620–1627. DOI: 10.1093/ndt/gfx313.
36. 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, doubleblind, randomized, placebo-controlled trial. Am J Kidney Dis. 2015;66(6):945–950. DOI: 10.1053/j.ajkd.2015.05.017.
37. Alicic R.Z., Rooney M.T., Tuttle K.R. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017;12(12):2032–2045. DOI: 10.2215/CJN.11491116.
38. Chobanian A.V., Bakris G.L., Black H.R. et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206–1252. DOI: 10.1161/01.HYP.0000107251.49515.c2.
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