Journal List > J Rheum Dis > v.26(2) > 1122078

Ahn, Lee, Lee, Lee, and So: Comparison of Efficacy and Safety of Febuxostat in Gout Patients with Chronic Kidney Disease Stage 3 and Stage 4/5

Abstract

Objective

To compare efficacy and safety of febuxostat in gouty patients with chronic kidney disease (CKD) stage 3 and stage 4/5.

Methods

Age and sex matched patients with CKD stage 3 and stage 4/5 who were diagnosed with gout were included. The dose of febuxostat was increased according to serum uric acid (sUA) level. Adherence, the number of gout attack, the change of sUA, the change of estimated glomerular filtration rate (eGFR) and adverse events (AEs) were evaluated for 12 months.

Results

There were no significant differences in the baseline variables between CKD stage 3 and CKD stage 4/5. Disease duration was longer and baseline sUA was higher in the CKD stage 4/5. There were no significant differences in the mean sUA at the last follow-up, the number of patients who reached the sUA target of 6 mg/dL and the number of gout attack between the groups. There were no significant differences in the change of eGFR and decrease of eGFR between the groups. There were 2 cases of AEs. One patient in CKD stage 3 had maculopapular rash and one patient in CKD stage 4/5 had dizziness. The AEs were subsided after febuxostat was stopped.

Conclusion

Febuxostat was efficacious and well tolerated in gout patients with CKD stage 4/5.

REFERENCES

1. Schlesinger N. Difficult-to-treat gouty arthritis: a disease warranting better management. Drugs. 2011; 71:1413–39.
2. Fuldeore MJ, Riedel AA, Zarotsky V, Pandya BJ, Dabbous O, Krishnan E. Chronic kidney disease in gout in a managed care setting. BMC Nephrol. 2011; 12:36.
crossref
3. McClory J, Said N. Gout in women. Med Health R I. 2009; 92:363–4. 368.
4. Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum. 2004; 51:321–5.
crossref
5. 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; 76:29–42.
crossref
6. Richette P, Frazier A, Bardin T. Pharmacokinetics considerations for gout treatments. Expert Opin Drug Metab Toxicol. 2014; 10:949–57.
crossref
7. Dalbeth N, Kumar S, Stamp L, Gow P. Dose adjustment of allopurinol according to creatinine clearance does not provide adequate control of hyperuricemia in patients with gout. J Rheumatol. 2006; 33:1646–50.
8. Mukoyoshi M, Nishimura S, Hoshide S, Umeda S, Kanou M, Taniguchi K, 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; 38:496–510.
9. Hira D, Chisaki Y, Noda S, Araki H, Uzu T, Maegawa H, et al. Population pharmacokinetics and therapeutic efficacy of Febuxostat in patients with severe renal impairment. Pharmacology. 2015; 96:90–8.
crossref
10. Schumacher HR Jr, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J, 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; 59:1540–8.
crossref
11. Juge PA, Truchetet ME, Pillebout E, Ottaviani S, Vigneau C, Loustau C, 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; 84:595–8.
crossref
12. Quilis N, Andrés M, Gil S, Ranieri L, Vela P, Pascual E. Febuxostat for patients with gout and severe chronic kidney disease: which is the appropriate dosage? Comment on the article by Saag et al. Arthritis Rheumatol. 2016; 68:2563–4.
crossref
13. Lim DH, Oh JS, Ahn SM, Hong S, Kim YG, Lee CK, et al. Febuxostat in hyperuricemic patients with advanced CKD. Am J Kidney Dis. 2016; 68:819–21.
crossref
14. Sakai Y, Otsuka T, Ohno D, Murasawa T, Sato N, Tsuruoka S. Febuxostat for treating allopurinol-resistant hyperuricemia in patients with chronic kidney disease. Ren Fail. 2014; 36:225–31.
crossref
15. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yü TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977; 20:895–900.
crossref
16. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130:461–70.
17. Saag KG, Whelton A, Becker MA, MacDonald P, Hunt B, Gunawardhana L. Impact of Febuxostat on renal function in gout patients with moderate-to-severe renal impairment. Arthritis Rheumatol. 2016; 68:2035–43.
crossref
18. Sircar D, Chatterjee S, Waikhom R, Golay V, Raychaudhury A, Chatterjee S, et al. Efficacy of Febuxostat for slowing the GFR decline in patients with CKD and asymptomatic hyperuricemia: a 6-month, double-blind, randomized, place-bo-controlled trial. Am J Kidney Dis. 2015; 66:945–50.
crossref
19. Lee S, So MW. Adherence with urate-lowering therapies among male patients with gout in a routine clinical setting. Mod Rheumatol. 2016; 26:950–5.
crossref

Figure 1.
Flow of the patients through the trial. CKD: chronic kidney disease.
jrd-26-118f1.tif
Table 1.
Baseline characteristics of the patients
Characteristics CKD 3 (n=48) CKD 4/5 (n=48) p-value
Age (yr) 66.9±12.7 67.1±12.6 0.923
Gender, male 36 (75.0) 36 (75.0) 1.000
Smoking, current 2 (4.2) 4 (8.3) 0.677
Alcohol drinking Comorbidities 12 (25.0) 10 (20.8) 0.809
Hypertension 38 (79.2) 44 (91.7) 0.146
Diabetes mellitus 12 (25.0) 4 (8.3) 0.053
Cardiac disease 26 (54.2) 18 (37.5) 0.151
History of malignancy 6 (12.5) 6 (12.5) 1.000
Diuretics use 14 (29.2) 24 (50.0) 0.060
Aspartate aminotransferase (IU/L) 30±8.4 32±8.2 0.902
Alanine aminotransferase (IU/L) 27±7.2 29±8.0 0.819
Gout characteristics
Disease duration (mo) 39.5±51.8 84.0±95.4 0.008
Switch from allopurinol 12 (25.0) 6 (12.5) 0.190
Baseline sUA (mg/dL) 8.9±1.8 9.8±2.7 0.049
Renal characteristics
Baseline eGFR (mL/min/1.73 m2) 46.3±9.0 18.3±7.7 0.000

Values are presented as mean±standard deviation or number (%). CKD: chronic kidney disease, sUA: serum uric acid, eGFR: estimated glomerular filtration rate.

Table 2.
Outcomes analysis of the patients
Outcomes CKD 3 (n=37) CKD 4/5 (n=35) p-value
Gout characteristics
Final dose of febuxostat (mg/dL) 46.5±14.9 42.3±9.4 0.159
Number of gout attack 0.9±1.0 0.7±0.8 0.719
Final sUA (mg/dL) 4.9±1.3 5.0±2.1 0.942
Final sUA <6.0 mg/dL 28 (75.7) 28 (80.0) 0.779
Renal characteristics
Change of eGFR (mL/min/1.73 m2) −0.6±4.8 0.0±5.8 0.649
Decrease of eGFR 19 (51.4) 23 (65.7) 0.241
Adverse event 1 (2.6) 1 (2.8) 1.000

Values are presented as mean±standard deviation or number (%). CKD: chronic kidney disease, sUA: serum uric acid, eGFR: estimated glomerular filtration rate.

Table 3.
Outcomes analysis of the patients (after exclusion of patients on hemodialysis)
Outcomes CKD 3 (n=37) CKD 4/5 (n=26) p-value
Gout characteristics
Final dose of febuxostat (mg/dL) 46.5±14.9 43.1±10.9 0.299
Number of gout attack 0.9±1.0 0.6±0.8 0.264
Final sUA (mg/dL) 4.9±1.3 4.4±1.5 0.157
Final sUA <6.0 mg/dL 28 (75.7) 22 (84.6) 0.531
Renal characteristics
Change of eGFR (mL/min/1.73 m2) −0.6±4.8 −0.6±6.5 0.988
Decrease of eGFR 19 (51.4) 16 (61.5) 0.452
Adverse event 1 (2.6) 0 (0.0) 1.000

Values are presented as mean±standard deviation or number (%). CKD: chronic kidney disease, sUA: serum uric acid, eGFR: estimated glomerular filtration rate.

TOOLS
Similar articles