Disease activity, pANCA and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis

Introduction: We analysed efficacy and predictors of response to anti-TNF-α antibody induction therapy using infliximab (IFX) in patients with moderate-to-severe ulcerative colitis (UC) in a large single center cohort.

Methods: A total of 90 IFX-treated UC patients was analysed retrospectively. For evaluation of disease activity, the colitis activity index (CAI) was calculated. Genotyping for UC-associated variants in the IL23R gene and 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 51.3% were in remission. At week 14 (after three IFX 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 5.1at week 2 (p<0.001), 4.4at week 6 (p<0.001), and 5.0at week 14 (p<0.001). Similarly, IFX therapy significantly decreased markers of systemic inflammation such as C-reactive protein levels and leukocyte counts (p=0.01 and p=0.001, respectively; week 2 vs. week 0). Multivariate regression analysis identified high CAI before IFX therapy (p=0.01) and negative pANCA status (p=0.01) as independent positive predictors for response to IFX. Homozygous carriers of IBD risk-increasing IL23R variants were more likely to respond to IFX than homozygous carriers of IBD risk-decreasing IL23R variants (74.1% vs. 34.6%; p=0.001). In contrast, there were no significant differences between responders and non-responders regarding the distribution of IL2/IL21 genotypes. No serious adverse IFX-related event requiring hospitalization was recorded.

Conclusion: Patients with moderate-to-severe UC can be effectively and safely treated with IFX. A high CAI before IFX therapy, pANCA seropositivity, and the IL23R genotype are predictors of early response to IFX.