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

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

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Alcoholic Hepatitis
Multicenter Studies
Placebos
Mortality
End Stage Liver Disease
Therapeutics
Tumor Necrosis Factor-alpha
Etanercept
Subcutaneous Injections
Demography
Cytokines
Morbidity

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Boetticher, N. C., Peine, C. J., Kwo, P., Abrams, G. A., Patel, T., Aqel, B., ... 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

A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Etanercept in the Treatment of Alcoholic Hepatitis. / Boetticher, Nicholas C.; Peine, Craig J.; Kwo, Paul; Abrams, Gary A.; Patel, Tushar; Aqel, Bashar; Boardman, Lisa; Gores, Gregory J.; Harmsen, William S.; McClain, Craig J.; Kamath, Patrick S.; Shah, Vijay H.

In: Gastroenterology, Vol. 135, No. 6, 12.2008, p. 1953-1960.

Research output: Contribution to journalArticle

Boetticher, NC, Peine, CJ, Kwo, P, Abrams, GA, Patel, T, Aqel, B, Boardman, L, Gores, GJ, Harmsen, WS, McClain, CJ, Kamath, PS & Shah, VH 2008, 'A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Etanercept in the Treatment of Alcoholic Hepatitis', Gastroenterology, vol. 135, no. 6, pp. 1953-1960. https://doi.org/10.1053/j.gastro.2008.08.057
Boetticher, Nicholas C. ; Peine, Craig J. ; Kwo, Paul ; Abrams, Gary A. ; Patel, Tushar ; Aqel, Bashar ; Boardman, Lisa ; Gores, Gregory J. ; Harmsen, William S. ; McClain, Craig J. ; Kamath, Patrick S. ; Shah, Vijay H. / A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Etanercept in the Treatment of Alcoholic Hepatitis. In: Gastroenterology. 2008 ; Vol. 135, No. 6. pp. 1953-1960.
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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.",
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AU - Kwo, Paul

AU - Abrams, Gary A.

AU - Patel, Tushar

AU - Aqel, Bashar

AU - Boardman, Lisa

AU - Gores, Gregory J.

AU - Harmsen, William S.

AU - McClain, Craig J.

AU - Kamath, Patrick S.

AU - Shah, Vijay H.

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N2 - 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.

AB - 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.

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