A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Etanercept in the Treatment of Alcoholic Hepatitis

Nicholas C. Boetticher, Craig J. Peine, Paul Kwo, Gary A. Abrams, Tushar Patel, Bashar Aqel, Lisa Boardman, Gregory J. Gores, William S. Harmsen, Craig J. McClain, Patrick S. Kamath, Vijay H. Shah

Research output: Contribution to journalArticle

216 Scopus citations

Abstract

Background & Aims: Alcoholic hepatitis is a cause of major morbidity and mortality that lacks effective therapies. Both experimental and clinical evidence indicate that the multifunctional cytokine tumor necrosis factor-α (TNF-α) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis. A pilot study demonstrated that the TNF-α-neutralizing molecule etanercept could be an effective treatment for patients with alcoholic hepatitis. Methods: Forty-eight patients with moderate to severe alcoholic hepatitis (Model for End-Stage Liver Disease score ≥15) were enrolled and randomized to groups that were given up to 6 subcutaneous injections of either etanercept or placebo for 3 weeks. Primary study end points included mortality at 1- and 6-month time points. Results: There were no significant baseline differences between the placebo and etanercept groups in demographics or disease severity parameters including age, gender, and Model for End-Stage Liver Disease score. The 1-month mortality rates of patients receiving placebo and etanercept were similar on an intention-to-treat basis (22.7% vs 36.4%, respectively; OR, 1.8; 95% CI, 0.5-6.5). The 6-month mortality rate was significantly higher in the etanercept group compared with the placebo group (57.7% vs 22.7%, respectively; OR, 4.6; 95% CI, 1.3-16.4; P = .017). Rates of infectious serious adverse events were significantly higher in the etanercept group compared with the placebo group (34.6% vs 9.1%, respectively, P = .04). Conclusions: In patients with moderate to severe alcoholic hepatitis, etanercept was associated with a significantly higher mortality rate after 6 months, indicating that etanercept is not effective for the treatment of patients with alcoholic hepatitis.

Original languageEnglish (US)
Pages (from-to)1953-1960
Number of pages8
JournalGastroenterology
Volume135
Issue number6
DOIs
StatePublished - Dec 2008

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Boetticher, N. C., Peine, C. J., Kwo, P., Abrams, G. A., Patel, T., Aqel, B., Boardman, L., Gores, G. J., Harmsen, W. S., McClain, C. J., Kamath, P. S., & Shah, V. H. (2008). A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Etanercept in the Treatment of Alcoholic Hepatitis. Gastroenterology, 135(6), 1953-1960. https://doi.org/10.1053/j.gastro.2008.08.057