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A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy.

Publication ,  Journal Article
Pockros, PJ; Patel, K; O'Brien, C; Tong, M; Smith, C; Rustgi, V; Carithers, RL; McHutchison, JG; Olek, E; Debruin, MF
Published in: Hepatology
June 2003

Recombinant human interleukin 12 (IL-12) is an immunomodulatory cytokine that is active against several viruses. Treatment options in patients with chronic hepatitis C with nonresponse to interferon (IFN)-based therapy are limited. Prior dose-ranging studies have indicated drug tolerability and transient suppression of hepatitis C virus (HCV) RNA by IL-12. The aim of this study was to determine the safety and efficacy of prolonged IL-12 therapy in patients who have failed treatment with IFN-alpha +/- ribavirin. A total of 225 patients at 21 U.S. sites who had a history of nonresponse to IFN-alpha or combination IFN-alpha plus ribavirin for treatment of HCV were randomized to 500 ng/kg IL-12 or placebo subcutaneously twice weekly for 12 weeks. The groups were then unblinded; patients receiving IL-12 continued for another 36 weeks, and the placebo group received 48 weeks of treatment with IL-12 in an open-label fashion. HCV RNA, serum alanine aminotransferase (ALT) level, and a repeat liver biopsy were assessed at 24 weeks following therapy. Approximately 1% (2 of 160) of nonresponsive patients enrolled for treatment had a sustained virologic response to IL-12 therapy, but 3% (7 of 225) developed severe adverse events probably related to treatment, resulting in early termination of the trial. Common adverse effects reported by most patients included chills, fever, fatigue, headache, and arthralgia. At termination of the study, 160 patients had received at least 8 weeks of treatment with IL-12. Paired liver biopsy specimens were available for evaluation in 54 patients, but there were no significant changes in Knodell fibrosis or histologic activity index (HAI) scores. In conclusion, IL-12 as monotherapy at the doses used in this trial for chronic hepatitis C has low efficacy, was poorly tolerated, and is unlikely to provide an alternative to conventional IFN-based therapy.

Duke Scholars

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

June 2003

Volume

37

Issue

6

Start / End Page

1368 / 1374

Location

United States

Related Subject Headings

  • Treatment Failure
  • Retreatment
  • Recombinant Proteins
  • RNA, Viral
  • Middle Aged
  • Male
  • Interleukin-12
  • Humans
  • Hepatitis C, Chronic
  • Hepacivirus
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pockros, P. J., Patel, K., O’Brien, C., Tong, M., Smith, C., Rustgi, V., … Debruin, M. F. (2003). A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy. Hepatology, 37(6), 1368–1374. https://doi.org/10.1053/jhep.2003.50242
Pockros, Paul J., Keyvr Patel, Christopher O’Brien, Myron Tong, Coleman Smith, Vinod Rustgi, Robert L. Carithers, John G. McHutchison, Elizabeth Olek, and Michael F. Debruin. “A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy.Hepatology 37, no. 6 (June 2003): 1368–74. https://doi.org/10.1053/jhep.2003.50242.
Pockros PJ, Patel K, O’Brien C, Tong M, Smith C, Rustgi V, et al. A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy. Hepatology. 2003 Jun;37(6):1368–74.
Pockros, Paul J., et al. “A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy.Hepatology, vol. 37, no. 6, June 2003, pp. 1368–74. Pubmed, doi:10.1053/jhep.2003.50242.
Pockros PJ, Patel K, O’Brien C, Tong M, Smith C, Rustgi V, Carithers RL, McHutchison JG, Olek E, Debruin MF. A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy. Hepatology. 2003 Jun;37(6):1368–1374.
Journal cover image

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

June 2003

Volume

37

Issue

6

Start / End Page

1368 / 1374

Location

United States

Related Subject Headings

  • Treatment Failure
  • Retreatment
  • Recombinant Proteins
  • RNA, Viral
  • Middle Aged
  • Male
  • Interleukin-12
  • Humans
  • Hepatitis C, Chronic
  • Hepacivirus