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Randomized Controlled Trial
. 2008 Dec;135(6):1953-60.
doi: 10.1053/j.gastro.2008.08.057. Epub 2008 Sep 13.

A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis

Nicholas C Boetticher  1 , 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
Affiliations
Randomized Controlled Trial

A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis

Nicholas C Boetticher et al. Gastroenterology. 2008 Dec.

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-alpha (TNF-alpha) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis. A pilot study demonstrated that the TNF-alpha-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 > or = 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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Conflict of interest statement

Author Disclosure: This study was funded through the NIH (R01 AA013933 to VS), the NIH funded Mayo Clinical Research Unit (CTSA), and Amgen (to VS), which provided study drug, and partially defrayed costs for cytokine analyses that exceeded the NIH budget. All analyses and writing were conducted at Mayo Clinic. Authors have no other conflicts of interest to disclose.

Figures

Figure 1
Figure 1. Flow diagram
Flow of participants through each stage of the trial is shown.
Figure 2
Figure 2. Kaplan Meier Survival Analysis
30-day mortality (vertical hashed line) was not significantly different between placebo (solid line) and etanercept (hashed line) groups. 6-month mortality rate was significantly higher in the etanercept arm compared to the placebo arm (p<0.05).
See this image and copyright information in PMC

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