Despite huge progress in the outpatient management of ulcerative colitis, there are still around 2,500 admissions for acute severe UC in the UK every year. Our current standard initial therapy (intravenous corticosteroids) is based upon the landmark trial of Truelove and Witt in the 1950s; advances since have been restricted to rescue therapy for those failing this initial care. Led by Tim Raine and Arthur Kaser in Cambridge, with a team of researchers from across the UK, the IASO trial will be a multicentre, randomised, double-blind, placebo-controlled trial to test the hypothesis that IL-1 blockade using anakinra, a safe and affordable antagonist of the IL-1 receptor, can improve outcomes when given as initial therapy in acute severe UC alongside corticosteroids. Funding for IASO has been provided by the NIHR and MRC through the EME programme, with additional funding from the Wellcome Trust and Swedish Orphan Biovitrum, totalling in all in excess of £1.6m. IASO will set this major clinical trial in the context of a detailed scientific study of the largest cohort of patients with acute severe UC ever assembled. Patient recruitment will begin in 2017, with final trial reporting expected in 2021/22.