Back to Search
Start Over
Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis.
- Source :
-
The American journal of gastroenterology [Am J Gastroenterol] 2010 Aug; Vol. 105 (8), pp. 1811-9. Date of Electronic Publication: 2010 Mar 02. - Publication Year :
- 2010
-
Abstract
- Objectives: We analyzed the efficacy and safety of the antitumor necrosis factor-alpha antibody infliximab (IFX) for induction therapy in patients with moderate-to-severe ulcerative colitis (UC) in a large single-center cohort.<br />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 the IL23R gene and in the IL2/IL21 region was performed.<br />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 and P=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-increasing IL23R variants were more likely to respond to IFX than were homozygous carriers of IBD risk-decreasing IL23R variants (74.1 vs. 34.6%; P=0.001). No serious adverse IFX-related events requiring hospitalization were recorded.<br />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 the IL23R genotype were predictors of early response to IFX.
- Subjects :
- Adult
Biomarkers analysis
Colectomy statistics & numerical data
Colitis, Ulcerative genetics
Colitis, Ulcerative immunology
Colitis, Ulcerative pathology
Enzyme-Linked Immunosorbent Assay
Female
Genetic Variation
Genotype
Humans
Infliximab
Logistic Models
Male
Remission Induction
Retrospective Studies
Treatment Outcome
Antibodies, Antineutrophil Cytoplasmic analysis
Antibodies, Monoclonal therapeutic use
Colitis, Ulcerative drug therapy
Gastrointestinal Agents therapeutic use
Receptors, Interleukin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1572-0241
- Volume :
- 105
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The American journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 20197757
- Full Text :
- https://doi.org/10.1038/ajg.2010.95