P431 Colonic Treg levels are reduced in patients with ulcerative colitis achieving clinical remission, but are not differentially affected by etrolizumab dose
Fuh F., Tew W., Keir M., Looney C., Maciuca R., McBride J., Ramirez-Montagut T.
Genentech, South San Francisco, United States
Etrolizumab, an anti-β7 mAb targeting integrins α4β7 and αEβ7, showed efficacy and safety compared with placebo (PBO) at induction in patients (pts) with moderate-to-severe ulcerative colitis (UC) in the phase 2 EUCALYPTUS trial. The percentage of pts achieving clinical remission was numerically lower with the higher dose of estrolizumab compared with the lower dose, which has been hypothesized to be due to dose-related inhibition of regulatory T-cell (Treg) migration to the colon. Using an epigenetic approach, we showed that etrolizumab treatment increased blood levels of CD3+ T cells and Tregs, compared with PBO (Fuh F et al. UEGW 2015). Here, we use the same approach to evaluate changes in cellular composition in colonic biopsies to explore the effect of etrolizumab dose on leukocyte infiltrate in the gut.
Epigenetic analyses were conducted in colonic biopsies taken from 60 EUCALYPTUS (Vermeire et al.
There were no significant changes from baseline in colonic Tregs, CD3+ T cells, Th17 cells, neutrophils/granulocytes, or B cells at wk 6 or wk 10 following treatment with etrolizumab or PBO. No significant differences were observed between pts treated with the low and high doses of etrolizumab. However, there was a significant reduction from baseline in colonic Tregs (
Pts treated with etrolizumab 100 mg had similar levels of colonic Tregs at wk 6 and wk 10 compared to pts treated with etrolizumab 300 mg. However, etrolizumab-treated remitters at wk 10 showed a significant reduction in Treg levels, suggesting that decreases in colonic Tregs may be associated with improvements in disease activity.