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Canadian Journal of Gastroenterology and Hepatology
Volume 28 (2014), Issue 1, Pages 35-40
http://dx.doi.org/10.1155/2014/367131
Original Article

Single-Dose Infliximab in Hepatitis C Genotype 1 Treatmentnaive Patients with High Serum Levels of Tumour Necrosis Factor-Alpha Does Not Influence the Efficacy of Pegylated Interferon Alpha-2B/Ribavirin Therapy

Curtis Cooper,1 Stephen Shafran,2 Susan Greenbloom,3 Robert Enns,4 John Farley,5 Nir Hilzenrat,6 Kurt Williams,7 Magdy Elkashab,8 Nabil Abadir,9 and Manuela Neuman10

1University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
2University of Alberta, Edmonton, Alberta, Canada
3Toronto Digestive Disease Associates, Toronto, Ontario, Canada
4St Paul’s Hospital, University of British Columbia, Canada
5Private Practice, Vancouver, British Columbia, Canada
6Jewish General Hospital and McGill University, Montreal, Quebec, Canada
7Royal University Hospital, Saskatoon, Saskatchewan, Canada
8Private practice, Toronto, Ontario, Canada
9Merck Canada Inc, Kirkland, Quebec, Canada
10University of Toronto, Toronto, Ontario, Canada

Received 10 September 2013; Accepted 15 September 2013

Copyright © 2014 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

BACKGROUND: Serum tumour necrosis factor-alpha (TNF-α) levels correlate negatively with hepatitis C virus (HCV) antiviral response.

OBJECTIVES: 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.

CONCLUSION: 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.