Clinical Drug Investigation

, Volume 39, Issue 8, pp 737–744 | Cite as

Appropriate Timing of Discontinuation of Tacrolimus Therapy for Refractory Ulcerative Colitis

  • Satohiro MatsumotoEmail author
  • Haruka Otake
  • Masanari Sekine
  • Takeshi Uehara
  • Hiroyuki Miyatani
  • Hirosato Mashima
Original Research Article


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.


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.


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.


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.


Compliance with Ethical Standards


No sources of funding were received for the preparation of this article.

Conflict of interest

Satohiro Matsumoto, Haruka Otake, Masanari Sekine, Takeshi Uehara, Hiroyuki Miyatani, and Hirosato Mashima have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

All procedures in this study were in accordance with the 1964 Helsinki Declaration (and its amendments). This study was conducted with the approval of The Etiological Study Ethical Review Board of Saitama Medical Center, Jichi Medical University.

Consent to participate

Patient consent was not required for this retrospective study.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Gastroenterology, Saitama Medical CenterJichi Medical UniversityOmiyaJapan

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