Risk of Febuxostat-Associated myopathy in patients with CKD

Chung Te Liu, Chun You Chen, Chien Yi Hsu, Po Hsun Huang, Feng Yen Lin, Jaw Wen Chen, Shing Jong Lin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background and objectives Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-assocated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain. Design, setting, participants, & measurements Our retrospective cohort study included 1332 patients using febuxostat in TaipeiMedicalUniversity-WanfangHospital fromFebruary of 2014 to January of 2016. The primary predictor was time-averaged eGFR as calculated by the equation proposed by the 2009 Chronic Kidney Disease Epidemiology Collaboration. The outcome was febuxostat-associated myopathy defined as elevated creatine kinase levels during febuxostat use that were not attributed to other muscular injuries. Results Themedian duration of febuxostat usewas 224 days (25th, 75th percentiles: 86, 441.5 days).Of 1332 study participants, 1222 (91.7%) had CKD; the median eGFR was 20.8 ml/min per 1.73 m2 (25th, 75th percentiles: 9.0, 35.4 ml/min per 1.73 m2). Forty-one of the participants had febuxostat-associated myopathy (3.2%). All patients with myopathy had CKD, and the incident rate was 0.013 (95% confidence interval, 0.01 to 0.02) events per 100 patient-days in patients withCKD. Of 41 patientswithmyopathy, 37 hadmyositis, and four had rhabdomyolysis. Myopathy resolved in 17 patients who withdrew from treatment and eight patients who continued febuxostat treatment. Among the evaluated predictors, multivariate analysis showed that only the lowest eGFR tertile was significantly associated withmyopathy in febuxostat users. The odds ratio of the lowest eGFR tertile to the highest tertile was 4.21 (95% confidence interval, 1.7 to 10.43). This finding remained consistent among subgroups stratified by age, sex, diabetes status, coronary artery disease, and statin or fibrate use. Conclusions Patients with severely reduced eGFR had higher risk of myopathy with treatment of febuxostat. Regular monitoring of creatine kinase level is suggested for early detection of febuxostat-associated myopathy, particularly in patients with CKD.

Original languageEnglish
Pages (from-to)744-750
Number of pages7
JournalClinical Journal of the American Society of Nephrology
Volume12
Issue number5
DOIs
Publication statusPublished - 2017

Fingerprint

Muscular Diseases
Rhabdomyolysis
Creatine Kinase
Febuxostat
Confidence Intervals
Fibric Acids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hyperuricemia
Xanthine Oxidase
Chronic Renal Insufficiency
Coronary Artery Disease
Epidemiology
Cohort Studies
Therapeutics
Multivariate Analysis
Retrospective Studies
Odds Ratio

Keywords

  • Chronic kidney disease
  • Confidence Intervals
  • Coronary artery disease
  • Creatine Kinase
  • Diabetes mellitus
  • Febuxostat
  • Fibric Acids
  • Glomerular filtration rate
  • Gout Suppressants
  • Humans
  • Hyperuricemia
  • Multivariate Analysis
  • Myopathy
  • Myositis
  • Odds Ratio
  • Renal Insufficiency, Chronic
  • Retrospective Studies
  • Rhabdomyolysis
  • Universities
  • Xanthine Oxidase

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

Cite this

Risk of Febuxostat-Associated myopathy in patients with CKD. / Liu, Chung Te; Chen, Chun You; Hsu, Chien Yi; Huang, Po Hsun; Lin, Feng Yen; Chen, Jaw Wen; Lin, Shing Jong.

In: Clinical Journal of the American Society of Nephrology, Vol. 12, No. 5, 2017, p. 744-750.

Research output: Contribution to journalArticle

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title = "Risk of Febuxostat-Associated myopathy in patients with CKD",
abstract = "Background and objectives Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-assocated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain. Design, setting, participants, & measurements Our retrospective cohort study included 1332 patients using febuxostat in TaipeiMedicalUniversity-WanfangHospital fromFebruary of 2014 to January of 2016. The primary predictor was time-averaged eGFR as calculated by the equation proposed by the 2009 Chronic Kidney Disease Epidemiology Collaboration. The outcome was febuxostat-associated myopathy defined as elevated creatine kinase levels during febuxostat use that were not attributed to other muscular injuries. Results Themedian duration of febuxostat usewas 224 days (25th, 75th percentiles: 86, 441.5 days).Of 1332 study participants, 1222 (91.7{\%}) had CKD; the median eGFR was 20.8 ml/min per 1.73 m2 (25th, 75th percentiles: 9.0, 35.4 ml/min per 1.73 m2). Forty-one of the participants had febuxostat-associated myopathy (3.2{\%}). All patients with myopathy had CKD, and the incident rate was 0.013 (95{\%} confidence interval, 0.01 to 0.02) events per 100 patient-days in patients withCKD. Of 41 patientswithmyopathy, 37 hadmyositis, and four had rhabdomyolysis. Myopathy resolved in 17 patients who withdrew from treatment and eight patients who continued febuxostat treatment. Among the evaluated predictors, multivariate analysis showed that only the lowest eGFR tertile was significantly associated withmyopathy in febuxostat users. The odds ratio of the lowest eGFR tertile to the highest tertile was 4.21 (95{\%} confidence interval, 1.7 to 10.43). This finding remained consistent among subgroups stratified by age, sex, diabetes status, coronary artery disease, and statin or fibrate use. Conclusions Patients with severely reduced eGFR had higher risk of myopathy with treatment of febuxostat. Regular monitoring of creatine kinase level is suggested for early detection of febuxostat-associated myopathy, particularly in patients with CKD.",
keywords = "Chronic kidney disease, Confidence Intervals, Coronary artery disease, Creatine Kinase, Diabetes mellitus, Febuxostat, Fibric Acids, Glomerular filtration rate, Gout Suppressants, Humans, Hyperuricemia, Multivariate Analysis, Myopathy, Myositis, Odds Ratio, Renal Insufficiency, Chronic, Retrospective Studies, Rhabdomyolysis, Universities, Xanthine Oxidase",
author = "Liu, {Chung Te} and Chen, {Chun You} and Hsu, {Chien Yi} and Huang, {Po Hsun} and Lin, {Feng Yen} and Chen, {Jaw Wen} and Lin, {Shing Jong}",
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AU - Liu, Chung Te

AU - Chen, Chun You

AU - Hsu, Chien Yi

AU - Huang, Po Hsun

AU - Lin, Feng Yen

AU - Chen, Jaw Wen

AU - Lin, Shing Jong

PY - 2017

Y1 - 2017

N2 - Background and objectives Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-assocated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain. Design, setting, participants, & measurements Our retrospective cohort study included 1332 patients using febuxostat in TaipeiMedicalUniversity-WanfangHospital fromFebruary of 2014 to January of 2016. The primary predictor was time-averaged eGFR as calculated by the equation proposed by the 2009 Chronic Kidney Disease Epidemiology Collaboration. The outcome was febuxostat-associated myopathy defined as elevated creatine kinase levels during febuxostat use that were not attributed to other muscular injuries. Results Themedian duration of febuxostat usewas 224 days (25th, 75th percentiles: 86, 441.5 days).Of 1332 study participants, 1222 (91.7%) had CKD; the median eGFR was 20.8 ml/min per 1.73 m2 (25th, 75th percentiles: 9.0, 35.4 ml/min per 1.73 m2). Forty-one of the participants had febuxostat-associated myopathy (3.2%). All patients with myopathy had CKD, and the incident rate was 0.013 (95% confidence interval, 0.01 to 0.02) events per 100 patient-days in patients withCKD. Of 41 patientswithmyopathy, 37 hadmyositis, and four had rhabdomyolysis. Myopathy resolved in 17 patients who withdrew from treatment and eight patients who continued febuxostat treatment. Among the evaluated predictors, multivariate analysis showed that only the lowest eGFR tertile was significantly associated withmyopathy in febuxostat users. The odds ratio of the lowest eGFR tertile to the highest tertile was 4.21 (95% confidence interval, 1.7 to 10.43). This finding remained consistent among subgroups stratified by age, sex, diabetes status, coronary artery disease, and statin or fibrate use. Conclusions Patients with severely reduced eGFR had higher risk of myopathy with treatment of febuxostat. Regular monitoring of creatine kinase level is suggested for early detection of febuxostat-associated myopathy, particularly in patients with CKD.

AB - Background and objectives Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-assocated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain. Design, setting, participants, & measurements Our retrospective cohort study included 1332 patients using febuxostat in TaipeiMedicalUniversity-WanfangHospital fromFebruary of 2014 to January of 2016. The primary predictor was time-averaged eGFR as calculated by the equation proposed by the 2009 Chronic Kidney Disease Epidemiology Collaboration. The outcome was febuxostat-associated myopathy defined as elevated creatine kinase levels during febuxostat use that were not attributed to other muscular injuries. Results Themedian duration of febuxostat usewas 224 days (25th, 75th percentiles: 86, 441.5 days).Of 1332 study participants, 1222 (91.7%) had CKD; the median eGFR was 20.8 ml/min per 1.73 m2 (25th, 75th percentiles: 9.0, 35.4 ml/min per 1.73 m2). Forty-one of the participants had febuxostat-associated myopathy (3.2%). All patients with myopathy had CKD, and the incident rate was 0.013 (95% confidence interval, 0.01 to 0.02) events per 100 patient-days in patients withCKD. Of 41 patientswithmyopathy, 37 hadmyositis, and four had rhabdomyolysis. Myopathy resolved in 17 patients who withdrew from treatment and eight patients who continued febuxostat treatment. Among the evaluated predictors, multivariate analysis showed that only the lowest eGFR tertile was significantly associated withmyopathy in febuxostat users. The odds ratio of the lowest eGFR tertile to the highest tertile was 4.21 (95% confidence interval, 1.7 to 10.43). This finding remained consistent among subgroups stratified by age, sex, diabetes status, coronary artery disease, and statin or fibrate use. Conclusions Patients with severely reduced eGFR had higher risk of myopathy with treatment of febuxostat. Regular monitoring of creatine kinase level is suggested for early detection of febuxostat-associated myopathy, particularly in patients with CKD.

KW - Chronic kidney disease

KW - Confidence Intervals

KW - Coronary artery disease

KW - Creatine Kinase

KW - Diabetes mellitus

KW - Febuxostat

KW - Fibric Acids

KW - Glomerular filtration rate

KW - Gout Suppressants

KW - Humans

KW - Hyperuricemia

KW - Multivariate Analysis

KW - Myopathy

KW - Myositis

KW - Odds Ratio

KW - Renal Insufficiency, Chronic

KW - Retrospective Studies

KW - Rhabdomyolysis

KW - Universities

KW - Xanthine Oxidase

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