Title: Oral p38 mitogen-activated protein kinase inhibition with BIRB 796 for active Crohn's disease: a randomized, double-blind, placebo-controlled trial
Authors: Schreiber, Stefan ×
Feagan, Brian
D'Haens, Geert
Colombel, Jean-Frederic
Geboes, Karel
Yurcov, Mikhail
Isakov, Vasily
Golovenko, Oleg
Bernstein, Charles N
Ludwig, Diether
Winter, Trevor
Meier, Ulrich
Yong, Chan
Steffgen, Jürgen #
Issue Date: Mar-2006
Series Title: Clinical Gastroenterology and Hepatology vol:4 issue:3 pages:325-34
Abstract: BACKGROUND & AIMS: The p38 mitogen-activated protein kinase (MAPK) regulates the expression of proinflammatory cytokines, which play a critical role in the pathophysiology of Crohn's disease (CD). This study investigated the efficacy and safety of BIRB 796, a highly potent inhibitor of p38 MAPK, in chronic active CD. METHODS: In a multicenter, multinational trial, 284 patients with moderate to severe CD were randomized to receive placebo, or 10, 20, 30, or 60 mg of BIRB 796 twice daily for 8 weeks. Clinical endpoints were based on standard safety assessments, CD Activity Index, C-reactive protein levels, and quality of life (Inflammatory Bowel Disease Questionnaire). In a substudy, the Crohn's Disease Endoscopic Index of Severity and histologic results of biopsy specimens were assessed. RESULTS: No clinical efficacy (primary end point, clinical remission; secondary end point, clinical response; Inflammatory Bowel Disease Questionnaire; Crohn's Disease Endoscopic Index of Severity) was seen for BIRB 796 in comparison with placebo. A significant, dose-dependent decrease of C-reactive protein level was observed transiently after BIRB 796 after 1 week with a return to baseline level over time. The incidence of adverse events was comparable between all treatment groups, with the exception of a mild increase of transaminase levels that was seen more frequently in the BIRB 796 groups. Geographic center effects were observed with Russian centers producing distinctly higher remission and response rates and lower adverse event rates than in other countries in both placebo and active treatment groups. CONCLUSIONS: There was no evidence for clinical efficacy of BIRB 796 in CD. A remarkable difference in the course of CD exists between Russia and non-Russian centers.
ISSN: 1542-3565
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science