Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis.
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.
Jürgens
Matthias
M
Department of Medicine II, Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.
Laubender
Rüdiger P
RP
Hartl
Franziska
F
Weidinger
Maria
M
Seiderer
Julia
J
Wagner
Johanna
J
Wetzke
Martin
M
Beigel
Florian
F
Pfennig
Simone
S
Stallhofer
Johannes
J
Schnitzler
Fabian
F
Tillack
Cornelia
C
Lohse
Peter
P
Göke
Burkhard
B
Glas
Jürgen
J
Ochsenkühn
Thomas
T
Brand
Stephan
S
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
D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D005765:Gastrointestinal Agents; C515500:IL23R protein, human; D018123:Receptors, Interleukin; D000069285:Infliximab