P468 Etrolizumab treatment improves histological activity as assessed by the Robarts histopathology index
Feagan B.G.1, De Hertogh G.2, Peyrin-Biroulet L.3, Rubin D.T.4, Maciuca R.5, McBride J.5, Arulmani U.*5, Scherl A.5
1University of Western Ontario, London, Canada 2University of Leuven, Leuven, Belgium 3Université de Lorraine, Vandœuvre-lès-Nancy, France 4University of Chicago Medicine, Chicago, United States 5Genentech, South San Francisco, United States
Etrolizumab, an anti-β7 mAb targeting α4β7 and αEβ7 integrins, showed efficacy and safety vs placebo (PBO) during 10 weeks of induction in patients with moderate-to-severe UC in the phase 2 trial, EUCALYPTUS. Because a reduction in histological inflammation has been linked with improved long-term clinical outcome (Bryant et al.
Patients were randomly assigned (1:1:1) to subcutaneous etrolizumab (100 mg at weeks 0, 4 and 8, with PBO at week 2, or 420-mg loading dose at week 0, followed by 300 mg at weeks 2, 4 and 8), or matching PBO. Biopsies were taken using flexible sigmoidoscopy/full colonoscopy from the most inflamed colonic area within 10–40 cm from the anal verge at baseline (BL) and at week 10. Batched H&E stained slides were scored by a single pathologist using the Geboes scale and converted to RHI (Mosli et al.
Analysis included 89 (of 119 efficacy-evaluable) patients with BL histological data and BL RHI >1. Mean week 10 RHI reduction was greater for etrolizumab- compared with PBO-treated patients regardless of previous aTNF experience, and a greater proportion of patients receiving etrolizumab achieved histological improvement compared with PBO. Of patients with an endoscopic subscore (ES) ≤1 at week 10, 89% experienced histological improvement. Mean (SD) RHI change was −14.2 (5.5) in patients with an ES ≤1 at week 10 versus −2.5 (9.5) in patients with an ES >1.
RHI-measured histological activity improved after 10 weeks of etrolizumab treatment. Consistent with the clinical remission rates observed in EUCALYPTUS, the magnitude of histological improvement was greater in the aTNF-naive vs aTNF-IR subgroup. RHI reductions are associated with improved ES at week 10.