title: Comparative safety study on severe anemia by simeprevir versus telaprevir-based triple therapy for chronic hepatitis C.
abstract: OBJECTIVE
  The addition of hepatitis C virus (HCV) NS3/4A protease inhibitors to the pegylated interferon (PEG-IFN) α and ribavirin combination regimen (triple therapy) has dramatically improved treatment outcome. Unfortunately, anemia remains a common adverse effect. This study was done to compare the development of severe anemia during simeprevir- or telaprevir-based triple therapy.
  
  
  METHODS
  This retrospective multicenter study consisted of 837 consecutive Japanese HCV genotype 1 patients treated in a real-world clinical setting, 811 of whom were enrolled (simeprevir 281, telaprevir 530). The inosine triphosphate pyrophosphatase (ITPA) genotype at rs1127354 was determined for all studied patients. Logistic regression was done after propensity score matching to assess the risk of development of severe anemia.
  
  
  RESULTS
  Propensity score matching of the entire study population yielded 266 matched pairs. Severe anemia (nadir hemoglobin < 9.0 g/dL) was developed during the treatment period by 81 (30.5%) and 144 (54.1%) patients treated with simeprevir and telaprevir, respectively. Treatment with simeprevir was independently associated with a lower risk of severe anemia (odds ratio 0.25, 95% confidence interval 0.16-0.38, P < 0.0001). Moreover, ITPA genotype, age, hemoglobin level, and estimated glomerular filtration rate at baseline were also independent factors associated with the development of severe anemia.
  
  
  CONCLUSIONS
  Patients treated with simeprevir-based triple therapy have a lower risk of the development of severe anemia than those treated with telaprevir. Moreover, ITPA genotype and age may be useful for individualizing treatment to reduce the risk of anemia-related adverse effects.
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.affiliation: Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kajiwara
authors.affiliation: The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nomura
authors.affiliation: Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawano
authors.affiliation: Department of Medicine, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Dohmen
authors.affiliation: Center for Liver Disease, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.affiliation: Department of Medicine, Fukuoka City Hospital, Fukuoka, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Koyanagi
authors.affiliation: Department of Medicine and Bioregulatory Science, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimoda
authors.affiliation: Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000367:Age Factors; D000368:Aged; D000740:Anemia / Q000139:chemically induced*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate; D006454:Hemoglobins; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects*; D011755:Pyrophosphatases / Q000235:genetics; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D012306:Risk; D012720:Severity of Illness Index; D000069616:Simeprevir / Q000008:administration & dosage / Q000009:adverse effects*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D000097630:Inosine Triphosphatase
chemical_list: D004791:Enzyme Inhibitors; D006454:Hemoglobins; D016898:Interferon-alpha; D009842:Oligopeptides; D011755:Pyrophosphatases; D012254:Ribavirin; D000069616:Simeprevir; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C486464:telaprevir; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase
keywords: anemia; hepatitis C virus; inosine triphosphatase; ribavirin; simeprevir