title: Single-dose infliximab in hepatitis C genotype 1 treatment-naive patients with high serum tumour necrosis factor-alpha does not influence the efficacy of pegylated interferon alpha-2b/ribavirin therapy.
abstract: BACKGROUND
  Serum tumour necrosis factor-alpha (TNF-α) levels correlate negatively with hepatitis C virus (HCV) antiviral response.
  
  
  OBJECTIVE
  To test the hypothesis that a single infliximab induction dose would positively influence on-treatment virological response and sustained virological response (SVR).
  
  
  METHODS
  The present study was a phase IIIB, randomized, prospective, open-label pilot trial conducted at eight Canadian sites. Treatment-naive HCV genotype 1-infected patients 18 to 65 years of age with high serum TNF-α values (>300 pg⁄mL) were randomly assigned to receive a single pretreatment induction infliximab infusion (5 mg⁄kg) seven days before antiviral therapy (arm A) or no pretreatment (arm B). All patients received pegylated interferon α2b (1.5 μg⁄kg⁄week) plus weight-based ribavirin (800 mg⁄day to 1400 mg⁄day) for up to 48 weeks.
  
  
  RESULTS
  Eighty-five patients (arm A [n=41], arm B [n=44]; 70% male) received pegylated interferon α2b. The mean age (48.1 years), race (81% white) and METAVIR fibrosis stage (F0-2 = 79%, F3-4 = 21%) were similar between groups. Infliximab was well tolerated without attributable severe adverse events; 56.5% completed the study (arm A [n=21], arm B [n=27]). Most discontinuations were due to virological failure at weeks 12 (n=20 [23.5%]) and 24 (n=7 [8.2%]) and did not differ according to group. Numerically lower proportions of infliximab recipients achieved rapid virological response (19.5% versus 36.4%), complete early virological response (43.9% versus 59.1%) and SVR (34.1% versus 52.3%). However, between-group differences did not reach statistical significance. No differences in adverse event profile or laboratory measures were noted.
  
  
  CONCLUSIONS
  A single infliximab dose before pegylated-interferon α2b and ribavirin therapy did not result in greater viral decline during the first 12 weeks of HCV therapy or improved SVR.
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: Stephan
authors.initials: S
authors.lastname: Shafran
authors.forename: Susan
authors.initials: S
authors.lastname: Greenbloom
authors.forename: Robert
authors.initials: R
authors.lastname: Enns
authors.forename: John
authors.initials: J
authors.lastname: Farley
authors.forename: Nir
authors.initials: N
authors.lastname: Hilzenrat
authors.forename: Kurt
authors.initials: K
authors.lastname: Williams
authors.forename: Magdy
authors.initials: M
authors.lastname: Elkashab
authors.forename: Nabil
authors.initials: N
authors.lastname: Abadir
authors.forename: Manuela
authors.initials: M
authors.lastname: Neuman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002170:Canada; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000069285:Infliximab; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D019562:Viral Load / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069285:Infliximab; C417083:peginterferon alfa-2b