Performance of tacrolimus in hospitalized patients with steroid-refractory acute severe ulcerative colitis

BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening 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.AIM To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis.METHODS 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.RESULTSIn 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. In36.4% 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.CONCLUSION 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 steroidrefractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.

Ustekinumab: “Real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease

BACKGROUND Ustekinumab was approved in Europe for the treatment of adults with moderate to severe Crohn's disease(CD)in 2016,and there is an urgent need for data on its everyday use.AIM To obtain data on the daily use of ustekinumab.METHODS This is a retrospective monocentric study.Patients with moderate to severe CD who began ustekinumab therapy at the inflammatory bowel diseases outpatient clinic of the Heidelberg University Hospital between December 2016 and March 2018 were selected based on electronic patient files.The primary study endpoint was combined steroid-free clinical remission or steroid-free clinical response at 24±6 wk of ustekinumab therapy.Secondary study endpoints were:achievement of mucosal healing,sonographic and magnetic resonance imaging response,biochemical response,the need for intestinal surgery within 24±6 wk after treatment initiation,the occurrence of adverse events,treatment discontinuation due to nonresponse or adverse events,improvement of extraintestinal manifestations,clinical response at 48±6 wk of therapy,and association of response with nucleotid oligodimerisation domain 2 mutations.RESULTS Fifty-seven patients with CD(5.3%anti-tumour necrosis factorαnaive,63.2%having undergone at least one intestinal surgery)were included in the study.Twenty patients(35.1%)achieved steroid-free clinical remission,6(10.5%)steroid-free clinical response and 31(54.4%)were non-responders.Treatment discontinuation due to adverse events occurred in two patients(3.5%).Male sex,the presence of extraintestinal manifestations and the use of steroids at baseline were predictors of nonresponse to ustekinumab therapy.CONCLUSION In a“real-world”treatment-refractory cohort of patients with CD,ustekinumab appeared efficacious and safe.