Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial.
OBJECTIVE
Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn's disease (CD). Adalimumab is a human immunoglobulin G1 (IgG(1)) monoclonal antibody targeting tumor necrosis factor (TNF). A randomized, double-blind, placebo-controlled, dose-ranging trial was performed to evaluate the efficacy of adalimumab induction therapy in patients with CD.


METHODS
A total of 299 patients with moderate to severe CD naive to anti-TNF therapy were randomized to receive subcutaneous injections at weeks 0 and 2 with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg or placebo. The primary endpoint was demonstration of a significant difference in the rates of remission at week 4 (defined as a Crohn's Disease Activity Index score <150 points) among the 80 mg/40 mg, 160 mg/80 mg, and placebo groups.


RESULTS
The rates of remission at week 4 in the adalimumab 40 mg/20 mg, 80 mg/40 mg, and 160 mg/80 mg groups were 18% (P = .36), 24% (P = .06), and 36% (P = .001), respectively, and 12% in the placebo group. Adverse events occurred at similar frequencies in all 4 treatment groups except injection site reactions, which were more common in adalimumab-treated patients.


CONCLUSIONS
Adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn's disease naive to anti-TNF therapy. The optimal induction dosing regimen for adalimumab in this study was 160 mg at week 0 followed by 80 mg at week 2. Adalimumab was well tolerated.
Hanauer
Stephen B
SB
Division of Gastroenterology, University of Chicago Medical Center, Illinois 60637, USA. shanauer@uchicago.edu
Sandborn
William J
WJ
Rutgeerts
Paul
P
Fedorak
Richard N
RN
Lukas
Milan
M
MacIntosh
Donald
D
Panaccione
Remo
R
Wolf
Douglas
D
Pollack
Paul
P
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010919:Placebos; D012449:Safety; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab