Randomized controlled trials comparing the efficacy of vedolizumab monotherapy with combination therapy of vedolizumab and an immunomodulator in patients with ulcerative colitis (UC) are lacking. Emerging pharmacokinetic data indicate that vedolizumab concentrations correlate with clinical outcomes, although the correlation may be less strong for vedolizumab compared with an anti-TNF agents. Associations between concomitant use of immunomodulators and decreased immunogenicity of vedolizumab have been reported, but this does not appear to translate into enhanced therapeutic effect of combination therapy, at least not based on present data. However, data are sparse and often based on post-hoc analyses. Future comparative effectiveness studies of patients with UC, naive to vedolizumab as well as immunomodulators, are needed. This might be of specific relevance for subgroups of UC patients, such as young men and the elderly, in whom combination versus monotherapy therapy may have a different risk-benefit ratio, given the risk of malignancy associated with immunomodulators. (C) 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).