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
Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a life-threatening medical condition requiring hospitalization and often colectomy. Despite the increasing choice of medical therapy options for ulcerative colitis, the condition remains a great challenge in the field of inflammatory bowel diseases (IBD). The performance of the calcineurin inhibitor tacrolimus in this clinical setting is insufficiently elucidated.
To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis.
We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of IBD. 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 retrieved from entirely computerized patient charts. The primary study endpoint was clinical response to tacrolimus therapy, resulting in discharge from the hospital. Secondary study endpoints were colectomy rate and time to colectomy, achievement of clinical remission under tacrolimus therapy, and the occurrence of side effects.
In the majority of the 22 included patients (68.2%), tacrolimus therapy was initiated intravenously and subsequently converted to oral administration. The treatment duration was 128 ± 28.5 d (mean ± SEM), and the patients were followed up for 705 ± 110 d after treatment initiation. Among all patients, 86.4% were discharged from the hospital under continued oral tacrolimus therapy. In 36.4% of the patients, the administration of tacrolimus resulted in clinical remission at some point during the treatment. Thirty-two percent of the patients underwent colectomy between 5 and 194 d after the initiation of tacrolimus treatment (mean: 97.4 ± 20.8 d). Colectomy-free survival rates at 1, 3, 6 and 12 mo after the initiation of tacrolimus therapy were 90.9%, 86.4%, 77.3% and 68.2%, respectively. The safety profile of tacrolimus was overall favorable. Only two patients discontinued the treatment due to side effects.
The short-term outcome of tacrolimus in steroid-refractory acute severe ulcerative colitis was beneficial, and side effects were rare. In all, tacrolimus therapy appears to be a viable option for short-term treatment of steroid-refractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.
Core tip: Steroid-refractory acute severe ulcerative colitis requires hospitalization and is frequently a risky tightrope walk between surgery and medical treatment. Whereas sufficient data has been provided over time to justify ciclosporin and infliximab as salvage therapies in this clinical scenario, guideline recommendations are still more reluctant towards tacrolimus due to the relative lack of data. However, tacrolimus may have advantages over ciclosporin especially due to its different toxicity profile. Our study provides more insight in the potential of tacrolimus in the strictly defined situation of steroid-refractory acute severe ulcerative colitis in hospitalized patients.