title: Risk of Febuxostat-Associated Myopathy in Patients with CKD.
abstract: OBJECTIVE
  Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-associated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain.
  
  
  METHODS
  Our retrospective cohort study included 1332 patients using febuxostat in Taipei Medical University-Wanfang Hospital from February 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
  The median duration of febuxostat use was 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 with CKD. Of 41 patients with myopathy, 37 had myositis, 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 with myopathy 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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wanfang Hospital.|Department of Internal Medicine, School of Medecine, College of Medicine and.
authors.forename: Chung-Te
authors.initials: CT
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Wan Fang Hospital, and.
authors.forename: Chun-You
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, School of Medecine, College of Medicine and.|Institutes of Clinical Medicine and.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University-Hospital Taipei, Taipei, Taiwan; and.
authors.forename: Chien-Yi
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Institutes of Clinical Medicine and.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Division of Cardiology, Department of Medicine and.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, School of Medecine, College of Medicine and.|Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University-Hospital Taipei, Taipei, Taiwan; and.
authors.forename: Feng-Yen
authors.initials: FY
authors.lastname: Lin
authors.affiliation: Pharmacology and.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Division of Cardiology, Department of Medicine and.|Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Board of Directors, Taipei Medical University, Taipei, Taiwan.|Institutes of Clinical Medicine and.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Division of Cardiology, Department of Medicine and.|Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003402:Creatine Kinase / Q000097:blood; D000069465:Febuxostat / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate; D006074:Gout Suppressants / Q000009:adverse effects*; D006785:Hospitals, University; D006801:Humans; D033461:Hyperuricemia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009135:Muscular Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D016017:Odds Ratio; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D006074:Gout Suppressants; D000069465:Febuxostat; D003402:Creatine Kinase
keywords: Confidence Intervals; Creatine Kinase; Febuxostat; Fibric Acids; Gout Suppressants; Humans; Hyperuricemia; Multivariate Analysis; Myositis; Odds Ratio; Renal Insufficiency, Chronic; Retrospective Studies; Universities; Xanthine Oxidase; chronic kidney disease; coronary artery disease; diabetes mellitus; febuxostat; glomerular filtration rate; myopathy; rhabdomyolysis