A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis.
OBJECTIVE
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.
Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA.
Nicholas C
NC
Boetticher
Craig J
CJ
Peine
Paul
P
Kwo
Gary A
GA
Abrams
Tushar
T
Patel
Bashar
B
Aqel
Lisa
L
Boardman
Gregory J
GJ
Gores
William S
WS
Harmsen
Craig J
CJ
McClain
Patrick S
PS
Kamath
Vijay H
VH
Shah
D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006519:Hepatitis, Alcoholic / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept