P547 Early modification of inflammatory burden through treatment with vedolizumab or adalimumab is predictive of long-term treatment success in patients with Ulcerative Colitis from the VARSITY Study

Schreiber , S.(1);Galinsky , K.(2);Aubrecht , J.(2);Juarez , J.(2);Agboton , C.(3);Loftus Jr , E.V.(4);Danese , S.(5);

(1)University Hospital Schleswig-Holstein, Department of Internal Medicine I, Kiel, Germany;(2)Takeda, Gastroenterology Drug Discovery Unit, Cambridge MA, United States;(3)Takeda Pharmaceuticals International, Global Medical Affairs, Zurich, Switzerland;(4)Mayo Clinic College of Medicine, Division of Gastroenterology and Hepatology, Rochester MN, United States;(5)IRCCS Ospedale and University Vita-Salute San Raffaele, Department of Gastroenterology, Milan, Italy;


Use of inflammatory biomarkers is common practice in ulcerative colitis (UC) management1. This study examined the utility of faecal calprotectin (FCP), C-reactive protein (CRP),  and albumin biomarkers and their combination, for predicting outcomes of clinical remission and disease control (composite of clinical, endoscopic and histologic disease activity measures2) in patients (pts) with UC under therapy with vedolizumab (VDZ) or adalimumab (ADA) in the VARSITY study.


VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-control trial evaluating VDZ (anti-α4β7 integrin) vs ADA (anti-tumour necrosis factor-α) treatment in pts aged 18–85 years with moderate-to-severe UC (NCT02497469; EudraCT:2015-000939-33). Pts received either VDZ IV infusions (300 mg) on Day 1 and at Weeks (WKs) 2, 6, 14, 22, 30, 38, and 46 or ADA SC injections (40 mg), total dose 160 mg at WK1, 80 mg at WK2, and 40 mg every 2 weeks thereafter until WK50. In this post hoc analysis of data from 769 pts, the probability of clinical remission (total Mayo score ≤2, no subscore >1) and disease control (pt-reported outcome-2 [PRO2, Mayo subscores of stool frequency and rectal bleeding]; Mayo endoscopic subscore ≤1 [endoscopic improvement], and Robarts Histopathology Index score <5, [absence of histologic active disease]) were assessed at WK52 based on baseline and WK14 levels of dichotomized FCP (high-risk: ≥100 µg/g), CRP (high-risk: ≥5mg/L), and albumin (high-risk: <45 g/L) including the composite of high-risk CRP and FCP termed ‘inflammatory burden’ (IB).


In comparison with biomarkers measured at baseline, FCP at WK14 was the most predictive of WK52 clinical remission after VDZ or ADA treatment3; WK14 FCP was also predictive of disease control using a combined endpoint of PRO2, endoscopy and histologic remission/response. VDZ-treated pts with low-risk FCP (<100 µg/g) at WK14 had a 76% chance of achieving WK52 clinical remission vs 35% for pts with high-risk FCP (70% vs 33% for ADA-treated pts with low and high-risk FCP, respectively). VDZ-treated pts with IB (high-risk levels of FCP and CRP) at WK14 had a 16% chance of clinical remission at WK52 vs a 57% probability for this endpoint in pts without IB at WK14; the risk difference for this composite biomarker was 42% (Table).


The addition of CRP to FCP as a composite biomarker of IB at WK14 after treatment initiation can be a useful negative predictor of pts who are likely to achieve significant long-term benefits, including remission and disease control, with VDZ or ADA treatment.  

References: 1. Turner D, et al. Gastroenterology 2021;160(5):1570-38. 2. Danese S, et al. J Crohn’s Colitis 2021;15(Suppl1):S305–S305. 3. Dulai PS, et al. Gastroenterology 2021;160(6):S-46-7.