Calcineurin Inhibitors in Ulcerative Colitis

Cyclosporine A and tacrolimus are potent immunosuppressive drugs that inhibit calcineurin, thereby resulting in profound suppression of T-cell activation. Randomized controlled trials demonstrated their efficacy in inducing remission in steroid-refractory and -dependent ulcerative colitis and both cyclosporine A and tacrolimus are considered medical rescue options for patients with acute severe ulcerative colitis resistant to corticosteroids, who otherwise would have to undergo colectomy. In contrast, calcineurin inhibitors are of limited value in the maintenance of remission, but rather act as bridging agents until maintenance therapy with other agents such as thiopurines becomes effective. Whereas cyclosporine A therapy is usually initiated as continuous intravenous infusion, tacrolimus can be given orally; however, both drugs display a narrow therapeutic window and frequent monitoring of drug levels is pivotal for both compounds. The advent of biological drugs expanded the therapeutic options in acute severe steroid resistant colitis and the choice of therapy should be guided by physician experience and consider patient characteristics and different adverse event profiles associated with both classes of compounds.