Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus

Background Intravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied. Aim To determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis. Methods Eighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks. Results Response rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus. Conclusions Patients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments.

PP180 Optimal Treatment Sequence For Targeted Immune Modulators For The Treatment Of Moderate To Severe Ulcerative Colitis

IntroductionSeveral targeted immune modulators (TIMs) have demonstrated effectiveness in moderate-to-severe ulcerative colitis, including adalimumab, golimumab, infliximab, infliximab biosimilars, tofacitinib, ustekinumab, and vedolizumab. In addition to assessing individual TIMs, evaluating TIM sequences can inform clinical care as well as coverage and reimbursement policies. Our objective was to identify optimal treatment sequences based on maximum net health benefit (NHB), lowest total cost (cost minimizing), quality-adjusted life-year (QALY) maximization, or convenience (avoidance of intravenous treatments), and to evaluate their cost effectiveness compared with conventional treatment from the health sector perspective.MethodsWe developed a Markov model with eight-week cycles and a lifetime time horizon. The health states were active, clinical response without remission, remission, and death. TIM efficacy was informed by a network meta-analysis conducted by the Institute for Clinical and Economic Review. Sequences were generated by ranking TIMs and then conventional treatment according to NHB, cost minimization, QALY maximization, or convenience and combining top ranked TIMs in the biologic naïve and biologic experienced populations. NHB was calculated at USD 150,000 per QALY. Probabilistic sensitivity analysis (PSA) was undertaken to estimate the probability of each sequence having the highest NHB rank, QALY maximizing rank, and cost-minimizing rank.ResultsTwenty-one sequences were evaluated. The sequence with the highest NHB was infliximab followed by tofacitinib (-0.12 QALYs), which also had the lowest incremental costs (USD37,266). For orally and subcutaneously administered TIMs, the sequence of golimumab-tofacitinib had the highest NHB (-0.34 QALYs). Ustekinumab-vedolizumab was not only the top ranked sequence as measured by QALY maximization (0.172 incremental QALYs), but it also had the highest total incremental cost (USD166,094). Results of the PSA were consistent with deterministic rankings for the top-ranking sequences and showed that the top two or three regimens were close in magnitude.ConclusionsThe optimal sequence with regard to NHB and cost minimization was infliximab or biosimilars, followed by tofacitinib, adalimumab, or vedolizumab. Sequences that generated the most QALYs began with ustekinumab, followed by vedolizumab, tofacitinib, and adalimumab.