Tacrolimus for the Treatment of Ulcerative Colitis

Abstract

Tacrolimus is a calcineurin inhibitor used for the treatment of corticosteroid-refractory ulcerative colitis (UC). Two randomized controlled trials and a number of retrospective studies have assessed the therapeutic effect of tacrolimus in UC patients. These studies showed that tacrolimus has excellent short-term efficacy in corticosteroid-refractory patients, with the rates of clinical response ranging from 61% to 96%. However, the long-term prognosis of patients treated with tacrolimus is disappointing, and almost 50% of patients eventually underwent colectomy in long-term follow-up. Tacrolimus can achieve mucosal healing in 40-50% of patients, and this is associated with a favorable long-term prognosis. Anti-tumor necrosis factor (TNF)-α antibodies are another therapeutic option in corticosteroid-refractory patients. A prospective head-to-head comparative study of tacrolimus and infliximab is currently being performed to determine which treatment is more effective in corticosteroid-refractory patients. Several retrospective studies have demonstrated that switching between tacrolimus and anti-TNF-α antibody therapy was effective in patients who were refractory to one of the treatments. Most adverse events of tacrolimus are mild; however, opportunistic infections, especially pneumocystis pneumonia, are the most important adverse events, and these should be carefully considered during treatment. Several issues on tacrolimus treatment in UC patients remain unsolved (e.g., use of tacrolimus as remission maintenance therapy). Further controlled studies are needed to optimize the use of tacrolimus for the treatment of UC.

A Phase 1, Multiple‐Dose Study of Vedolizumab in Japanese Patients With Ulcerative Colitis

“…In fact, distinct treatment outcomes for ulcerative colitis have been previously reported in Japanese patients for treatments including adalimumab, [24][25][26] leukocytapheresis, 27,28 and tacrolimus. 29,30 Therefore, it is important to investigate both the PK and PD for ulcerative colitis drugs in this population in separate clinical trials. Vedolizumab exhibited target-mediated drug disposition, and at concentrations below 1 μg/mL, the elimination was nonlinear, similar to that observed in non-Japanese patients, 16 which suggests similar expression levels of the α 4 β 7 integrin target across different populations.…”

Lactobacillus plantarum L15 Alleviates Colitis by Inhibiting LPS-Mediated NF-κB Activation and Ameliorates DSS-Induced Gut Microbiota Dysbiosis

“…Conventionally, UC can be treated with a number of medications, including 5-aminosalicylic acid drugs, steroids, and immunosuppressants. These therapies have a number of drawbacks, ranging from unpleasant reactions to high cost especially for patients who may need them for a long time frame ( 3 ). Therefore, it becomes important to find a healthy and effective way to manage UC.…”

Safety and Efficacy of Combination Treatment With Calcineurin Inhibitors and Vedolizumab in Patients With Refractory Inflammatory Bowel Disease

“…2 In CD, reports of rapid response to intravenous (IV) and oral cyclosporin also have been reported with response rates up to 59%. 4,5 Tacrolimus also shows excellent short-term efficacy in IBD with short-term response rates of 61% to 96% in UC, 6 and partial and complete response rates of 39% and 29% in CD. 7 However, despite this evidence, protracted use of calcineurin inhibitors is limited by adverse events including infection, nephrotoxicity, hypercholesterolemia, and hypertension, and long-term prognosis is poor with high relapse rates on cessation of therapy.…”

“…7 However, despite this evidence, protracted use of calcineurin inhibitors is limited by adverse events including infection, nephrotoxicity, hypercholesterolemia, and hypertension, and long-term prognosis is poor with high relapse rates on cessation of therapy. 4,6,8 Consequently, their use traditionally has been limited in IBD owing to a lack of an appropriate maintenance therapy.…”