title: Adjusting the starting dose of telaprevir according to renal function decreases adverse effects and affects the sustained virological response rate.
abstract: BACKGROUND
  Telaprevir (TVR) plays a major role in renal damage and anemia associated with TVR/pegylated interferon/ribavirin therapy for chronic hepatitis C. Adjusting the TVR starting dose may reduce these adverse effects. We aimed to determine whether adjusting the starting dose according to renal function reduces TVR-associated renal damage and anemia and affects the sustained virological response (SVR).
  
  
  METHODS
  Our study included 112 patients infected with hepatitis C genotype 1 treated with pegylated interferon/ribavirin/TVR triple therapy. The TVR starting dose adjusted according to renal function was calculated as TVR/unadjusted estimated glomerular filtration rate (eGFR) ratio=TVR/(eGFR×body surface area/1.73).
  
  
  RESULTS
  A TVR/unadjusted eGFR ratio of 32 or greater was a predictor of renal impairment and anemia in multivariate analysis (odds ratio 12.09, P<0.001, and OR 4.14, P<0.001, respectively). Patients with a TVR/unadjusted eGFR ratio of 32 or greater developed significant renal impairment and anemia (P<0.001 and P=0.002, respectively). SVR was significantly reduced in patients with a TVR/unadjusted eGFR ratio less than 23 versus 23 or greater (66.7 and 87.2%, respectively, P=0.045). SVR tended to increase stepwise [<23.0 (66.7%), ≥23 to <32 (84.8%), and ≥32 (89.6%), respectively]. The TVR/unadjusted eGFR ratio was correlated significantly with the serum TVR concentration (r=0.541, P<0.001).
  
  
  CONCLUSIONS
  Adjusting the TVR starting dose according to the TVR/unadjusted eGFR ratio decreased adverse effects and affected the SVR rate. The TVR starting dose should be adjusted by a TVR/unadjusted eGFR ratio of 23 or greater to less than 32 to safely achieve SVR.
authors.affiliation: aDepartment of Gastroenterology bDivision of Advanced Clinical Research for Viral Hepatitis and Liver Cancer, Fukuoka University Faculty of Medicine cDepartment of Hepatology, Japanese Red Cross Fukuoka Hospital dDepartment of Medicine, Hakujyuji Hospital eDepartment of Gastroenterology, Fukuoka City Medical Association Hospital, Fukuoka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Takata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Iwashita
authors.forename: Naoaki
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunimoto
authors.forename: Shizuka
authors.initials: S
authors.lastname: Kuno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukunaga
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yotsumoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Sakurai
authors.forename: Genryu
authors.initials: G
authors.lastname: Hirano
authors.forename: Keiji
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Shinya
authors.initials: S
authors.lastname: Nishizawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshikane
authors.forename: Akira
authors.initials: A
authors.lastname: Anan
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Takeyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Kaoru
authors.initials: K
authors.lastname: Iwata
authors.forename: Makoto
authors.initials: M
authors.lastname: Irie
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shakado
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sohda
authors.forename: Shotaro
authors.initials: S
authors.lastname: Sakisaka
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology; D000368:Aged; D000740:Anemia / Q000097:blood / Q000139:chemically induced*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate; D006454:Hemoglobins / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C417083:peginterferon alfa-2b