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Disease Activity, ANCA, andIL23RGenotype Status Determine Early Response to Infliximab in Patients With Ulcerative Colitis

Jürgens, Matthias, MD1; Laubender, Rüdiger P, MPH2; Hartl, Franziska1; Weidinger, Maria1; Seiderer, Julia, MD1; Wagner, Johanna1; Wetzke, Martin3; Beigel, Florian, MD1; Pfennig, Simone1; Stallhofer, Johannes1; Schnitzler, Fabian, MD1; Tillack, Cornelia, MD1; Lohse, Peter, MD4; Göke, Burkhard, MD1; Glas, Jürgen, MD, MSc1,5,6; Ochsenkühn, Thomas, MD1; Brand, Stephan, MD1

American Journal of Gastroenterology: August 2010 - Volume 105 - Issue 8 - p 1811–1819
doi: 10.1038/ajg.2010.95
ORIGINAL CONTRIBUTIONS: INFLAMMATORY BOWEL DISEASE
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OBJECTIVES: We analyzed the efficacy and safety of the antitumor necrosis factor-α antibody infliximab (IFX) for induction therapy in patients with moderate-to-severe ulcerative colitis (UC) in a large single-center cohort.

METHODS: A total of 90 UC patients treated with IFX for 14 weeks were analyzed retrospectively. Colitis activity index (CAI) and markers of inflammation were measured during IFX induction therapy. Genotyping for UC-associated variants in theIL23Rgene and in theIL2/IL21region was performed.

RESULTS: At week 2 (after the first IFX infusion), 64.1% of IFX-treated patients had clinical response to IFX and 52.6% were in remission. At week 14 (after three infusions), 61.0% showed clinical response and 52.5% were in remission. The mean CAI decreased significantly from 10.4 points at week 0 to 5.1 at week 2 (P<0.001), to 4.4 at week 6 (P<0.001), and to 5.0 at week 14 (P<0.001). Similarly, IFX therapy significantly decreased C-reactive protein levels and leukocyte counts (P=0.01 andP=0.001 at week 2 and week 0, respectively). Multivariate regression analysis identified high CAI before IFX therapy (P=0.01) and negative antineutrophil cytoplasmatic autoantibody (ANCA) status (P=0.01) as independent positive predictors for response to IFX. Homozygous carriers of inflammatory bowel disease (IBD) risk-increasingIL23Rvariants were more likely to respond to IFX than were homozygous carriers of IBD risk-decreasingIL23Rvariants (74.1 vs. 34.6%;P=0.001). No serious adverse IFX-related events requiring hospitalization were recorded.

CONCLUSIONS: Our findings suggest that IFX therapy is safe and effective in patients with moderate-to-severe UC. A high CAI before IFX therapy, ANCA seronegativity, and theIL23Rgenotype were predictors of early response to IFX.

1Department of Medicine II, Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany

2Institute for Medical Informatics, Biometry and Epidemiology (IBE), Ludwig-Maximilians-University Munich, Munich, Germany

3Department of Pediatrics, Medical School Hannover, Hannover, Germany

4Department of Clinical Chemistry, Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany

5Department of Preventive Dentistry and Periodontology, University of Munich, Munich, Germany

6Institute of Human Genetics, RWTH Aachen, Aachen, Germany

Correspondence: Stephan Brand, MD, Department of Medicine II, Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, D-81377 Munich, Germany. E-mail: stephan.brand@med.uni-muenchen.de

published online 2 March 2010

Received 10 July 2009; accepted 2 February 2010

SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg

© The American College of Gastroenterology 2010. All Rights Reserved.
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