title: Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Medicine II, Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Jürgens
authors.forename: Rüdiger P
authors.initials: RP
authors.lastname: Laubender
authors.forename: Franziska
authors.initials: F
authors.lastname: Hartl
authors.forename: Maria
authors.initials: M
authors.lastname: Weidinger
authors.forename: Julia
authors.initials: J
authors.lastname: Seiderer
authors.forename: Johanna
authors.initials: J
authors.lastname: Wagner
authors.forename: Martin
authors.initials: M
authors.lastname: Wetzke
authors.forename: Florian
authors.initials: F
authors.lastname: Beigel
authors.forename: Simone
authors.initials: S
authors.lastname: Pfennig
authors.forename: Johannes
authors.initials: J
authors.lastname: Stallhofer
authors.forename: Fabian
authors.initials: F
authors.lastname: Schnitzler
authors.forename: Cornelia
authors.initials: C
authors.lastname: Tillack
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Glas
authors.forename: Thomas
authors.initials: T
authors.lastname: Ochsenkühn
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
mesh_terms: D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D003082:Colectomy / Q000706:statistics & numerical data; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D000069285:Infliximab; D016015:Logistic Models; D008297:Male; D018123:Receptors, Interleukin / Q000235:genetics*; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D005765:Gastrointestinal Agents; C515500:IL23R protein, human; D018123:Receptors, Interleukin; D000069285:Infliximab