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

Abstract

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.