Published online Apr 7, 2019. doi: 10.3748/wjg.v25.i13.1603
Peer-review started: February 14, 2019
First decision: February 21, 2019
Revised: February 23, 2019
Accepted: March 11, 2019
Article in press: March 12, 2019
Published online: April 7, 2019
Steroid-refractory acute severe ulcerative colitis is a life-threatening medical condition requiring hospitalization and frequently emergency colectomy. Although there is a steadily growing choice of medications for ulcerative colitis, the treatment of steroid-refractory acute severe ulcerative colitis continues to be very challenging. Calcineurin inhibitors - mainly ciclosporin and tumor necrosis factor α (TNFα) antagonists have been shown to be viable therapeutic options to avoid colectomy in this scenario.
In contrast to that of ciclosporin, the performance of the calcineurin inhibitor tacrolimus in the clinical setting of steroid-refractory ulcerative colitis is insufficiently elucidated, but nonetheless recommended in national and international treatment guidelines for ulcerative colitis.
The objective of our study was to extend the current knowledge on the use of tacrolimus in steroid-refractory ulcerative colitis by assessing the short- and long-term outcomes of tacrolimus in adult inpatients suffering from steroid-refractory acute severe ulcerative colitis.
We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of inflammatory bowel diseases. All patients who were admitted to one of the wards of the Department of Gastroenterology and Hepatology of the Heidelberg University Hospital with acute severe ulcerative colitis between 2007 and 2018 and who received oral or intravenous tacrolimus for steroid-refractory disease were included. Baseline characteristics and data on the disease courses were obtained from entirely computerized patient charts. The key study endpoints were clinical response to tacrolimus therapy, colectomy rate, time to colectomy and the occurrence of side effects.
Our study revealed that intravenous or oral tacrolimus, as in previous studies by other authors ciclosporin and infliximab, was able to prevent emergency colectomy in the majority of adult inpatients with steroid-refractory acute severe ulcerative colitis. At the same time, the safety profile of high-dose tacrolimus in this setting was acceptable. However, colectomy rates due to therapy-refractory disease courses over the year following tacrolimus rescue therapy reached nearly one-third of the patients. These results are also comparable to those of other studies dealing with the use of ciclosporin or infliximab in steroid-refractory acute severe ulcerative colitis.
In all, tacrolimus appears to be a viable option for short-term treatment of steroid-refractory acute severe ulcerative colitis besides ciclosporin and anti-TNFα treatment.
Even though not recommended for long-term maintenance therapy in ulcerative colitis, tacrolimus is a valuable tool for the short-term treatment of steroid-refractory severe ulcerative colitis, where rapid induction of symptom relief is warranted to gain time for the introduction of other, more slowly acting substances, with more favorable long-term toxicity profiles. Prospective trials are required to define its role among other medications, and to examine the safety of an overlapping combined use with these medications.