Appropriate Timing of Discontinuation of Tacrolimus Therapy for Refractory Ulcerative Colitis

Background and Objectives Tacrolimus is very effective at inducing remission in patients with refractory ulcerative colitis. However, the optimal time-point for the discontinuation of tacrolimus is controversial because administration of tacrolimus for > 3 months is currently not approved for insurance reimbursement in Japan. We conducted this study to determine the optimal time of discontinuation of tacrolimus in patients with ulcerative colitis. Methods Of 38 patients who received tacrolimus as remission induction therapy for refractory active ulcerative colitis between 2009 and 2018, this study included 21 patients who received tacrolimus for ≥ 3 months before being switched to thiopurines. These patients were divided into two groups for analysis: the confirmed switch (CS) group ( n = 13), in which tacrolimus was switched to azathioprine after endoscopic confirmation of mucosal improvement, and the mandatory switch (MS) group ( n = 8), in which tacrolimus was switched to a thiopurine agent without endoscopic confirmation of improvement. Results The relapse rates after the switch to azathioprine were 23% and 88% in the CS and MS groups, respectively ( p = 0.0075). No patient of the CS group underwent surgery, while 50% of patients of the MS group underwent surgery ( p = 0.0117). The cumulative event-free rates at 6 months, 1 year, and 2 years were 92%, 92%, and 65%, respectively, in the CS group and 15%, 15%, and 0%, respectively, in the MS group ( p < 0.0001). The incidence rate of adverse reactions was 31% in the CS group and 13% in the MS group, but there were no serious adverse reactions. Conclusions It seems preferable to discontinue tacrolimus after endoscopic confirmation of mucosal healing. However, attention should be paid to the potential occurrence of adverse reactions associated with long-term tacrolimus therapy.