Background: Vedolizumab has been shown to induce clinical remission in patients with active ulcerative colitis. Treatment with anti-integrin vedolizumab leads to clinical remission in 16.9% and clinical response in 47.1% of cases after 6 weeks. However, in clinical practice, no decision to discontinue or continue vedolizumab therapy is made until 14 weeks at the earliest., Objective: The aim of this study is to develop an algorithm for optimizing vedolizumab administration in patients with moderate-to-severe ulcerative colitis by calculating the probability of clinical response at week 14, on the basis of the data from week 6., Methods: This is a prospective, single-arm, multicentric, noninterventional, observational study with no interim analyses and a sample size of 35 evaluable patients., Results: The enrollment started in August 2018 and was still open at the date of submission. The study is expected to complete in September 2020., Conclusions: The early identification of patients who are responding to an integrin antibody is therapeutically beneficial. At the same time, patients who are not responding can be identified earlier. The development of a therapeutic algorithm for identifying patients as responders or nonresponders can thus help prescribing physicians avoid ineffective treatments and stop these very early., (©Jimmi Cording, Margit Blömacher, Berit Inga Wiebe, Jost Langhorst, Torsten Kucharzik, Andreas Sturm, Stefan Schreiber, Ulf Helwig. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 08.11.2019.)