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.
RCT Entities:
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.
Authors: W J Sandborn; S B Hanauer; S Katz; M Safdi; D G Wolf; R D Baerg; W J Tremaine; T Johnson; N N Diehl; A R Zinsmeister Journal: Gastroenterology Date: 2001-11 Impact factor: 22.682
Authors: E Cabré; P Rodríguez-Iglesias; J Caballería; J C Quer; J L Sánchez-Lombraña; A Parés; M Papo; R Planas; M A Gassull Journal: Hepatology Date: 2000-07 Impact factor: 17.425
Authors: Alexander Wree; Matthew D McGeough; Maria Eugenia Inzaugarat; Akiko Eguchi; Susanne Schuster; Casey D Johnson; Carla A Peña; Lukas J Geisler; Bettina G Papouchado; Hal M Hoffman; Ariel E Feldstein Journal: Hepatology Date: 2017-12-28 Impact factor: 17.425