Fellermann1010. Fellermann K, Tanko Z, Herrlinger KR, Witthoeft T, Homann N, Bruening A, Ludwig D, Stange EF. Response of refractory colitis to intravenous or oral tacrolimus (FK506). Inflamm Bowel Dis . 2002;8:317-24.
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2002 |
Germany |
Moderate-to-severe colitis/steroid-refractory |
Truelove-Witts Score. Remission evaluation in 2 weeks. Follow up for 6 months |
38 |
IV Tacrolimus (0.01-0.02 mg/kg/day) or P.O. (0.1-0.2 mg/kg/day) |
Antibiotics; aminosalicilates; steroids; thiopurines |
28.94% (11/38) = clinical remission in 2 weeks. 16-month colectomy rate= 34% |
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Hogenauer1313. Hogenauer H, et al. Effect of oral tacrolimus (FK506) on steroid-refractory moderate/severe ulcerative colitis. Aliment Pharmacol Ther. 2003;18:415-23.
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2003 |
Austria |
Moderate-to-severe colitis/steroid-refractory |
Truelove Witts Score. Evaluation up to week 12 |
9 |
Tacrolimus 0.15 mg/kg/day (adjusted by serum target level: 10-20 ng/mL) |
Steroids; thiopurines |
66.66% (6/9) = clinical remission in 12 weeks. 3/9= 33.33% of colectomy on follow up |
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Baumgart44. Baumgart DC, Pintoffl J, Sturm A, Wiedenmann B, Dignass AU. Tacrolimus is safe and effective in patients with severe steroid-refractory or steroid-dependent inflammatory bowel disease- a long-term follow up. Am J Gastroenterol. 2006;101:1048-56.
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2006 |
Germany |
Steroid-dependent or refractory (57% pancolitis) |
Modified Clinical Activity Index up to 30 days |
40 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level: 4-8 ng/mL) |
Steroids |
45% (18/40) = clinical remission in 30 days; 77.5% (31/40) of clinical response. 22.5% colectomy on follow up |
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Ng2222. Ng SC, Arebi N, Kamm MA. Medium-term results of oral tacrolimus treatmentin refractory inflammatory bowel disease. Inflamm Bowel Dis . 2007;3:129-34.
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2007 |
England |
Steroid-dependent moderate-to-sevre colitis or previous failure to thiopurines or Infliximab |
Truelove Witts score up to 4 weeks |
6 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level: 5-10 ng/mL) |
Aminosalicilates; steroids; thiopurines; probiotics |
50% (3/6)= clinical remission in 4 weeks; 66.66% (4/6) of clinical response |
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Benson55. Benson A, Barrett T, Sparberg M, Buchman AL. Efficacy and safety of tacrolimus in refractory ulcerative colitis and crohn’s disease: a single center experience. Inflamm Bowel Dis. 2008;14:7-12.
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2007 |
USA |
Steroid-dependent or refractory moderate-to-severe colitis |
Clinical variables and progression to colectomy up to 29 weeks |
32 |
Tacrolimus 0.2 mg/kg/day (adjusted by serum target level:10-12 ng/mL) |
aminosalicilates; steroids; thiopurines |
9.37% (3/32)= clinical remission; 68.75% (22/32) of clinical response. 37.5%= colectomy on follow up |
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Yamamoto3232. Yamamoto S, Nakase H, Mikami S, Inoue S, Yoshino T, Takeda Y, et al. Long-term effect of tacrolimus therapy in patients with refractory ulcerative colitis. Aliment Pharmacol Ther . 2008;28:589-97.
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2008 |
Japan |
Moderate-to-severe colitis refractory to other treatments (81.5% pancolitis) |
Truelove Witts Score up to 30 days |
27 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
70.4% (19/27)= clinical remission in 30 days; 77.8% (21/27) of clinical response. 26.9%= colectomy on follow up |
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Thin3030. Thin LW, Murray K, Lawrance IC. Oral tacrolimus for the treatment of refractory inflammatory bowel diseasein the biologic era. Inflamm Bowel Dis . 2013;19:1490-8.
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2012 |
Australia |
Moderate-to-severe colitis refractory to other treatments |
Colitis Activity Index up to 30 days |
24 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:8-12 ng/mL) |
aminosalicilates; steroids |
37.5% clinical remission (9/24); 58.3% (14/24) clinical response |
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Schmidt2828. Schmidt KJ, Herrlinger KR, Emmrich J, Barthel D, Koc H, Lehnert H, Stange EF, Fellermann K, Buning J. Short-term efficacy of tacrolimus in steroid-refractory ulcerative colitis - experience in 130 patients. Aliment Pharmacol Ther . 2013;37:129-136.
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2013 |
Germany |
Steroid-refractory Moderate-to-severe colitis |
Lichtiger score up to 12 weeks; need for colectomy |
130 |
Tacrolimus 0.1 mg/kg/day |
aminosalicilates; steroids; thiopurines |
72% (94/130) clinical remission; 14% (18/130)= colectomy on follow up |
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Inoue1515. Inoue T, Murano M, Narabayashi K, Okada T, Nouda S, Ishida K, et al. The efficacy of oral tacrolimus in patients with moderate/severe ulcerative colitis not receiving concomitant corticosteroide therapy. Intern Med. 2013;52:15-20.
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2013 |
Japan |
Moderate-to-severe pancolitis without steroid treatment |
Lichtiger score. Mayo score for mucosal healing up to 4 weeks. |
11 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
aminosalicilates; thiopurines |
72.7% (8/11) clinical remission; 100% (11/11) clinical response |
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Miyoshi2121. Miyoshi J, Matsuoka K, Inoue N, Hisamatsu T, Ichikawa R, Yajima T, Okamoto S, Naganuma M, Sato T, Kanai T, Ogata H, Iwao Y, Hibi T. Mucosal healing with oral tacrolimus is associated with medium-nd long-term prognosis in steroid-refractory/dependent ulcerative colitis patients. J Crohn Colitis . 2013;7:e609-e614.
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2013 |
Japan |
Steroid-dependent or refractory moderate-to-severe colitis |
Lichtiger score. Mayo score for mucosal healing up to 12 weeks. |
51 |
Tacrolimus initial dose= 5 mg/day; then, oral Tacrolimus (adjusted by serum target level: 10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
39.2% (20/51)= clinical remission; 62.74% (32/51)= clinical response |
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Landy1717. Landy J, Wahed M, Peake STC, Hussein M, Ng SC, Lindsay JO, Hart AL. Oral tacrolimus s maintenance therapy for refractory ulcerative colitis - an analysis of outcomes in two London tertiary centers. J Crohn Colitis. 2013;7:e516-e521
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2013 |
England |
Moderate-to-severe colitis refractory to other treatments |
Truelove Witts Score up to 6 months |
25 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:5-10 ng/mL) |
aminosalicilates; steroids; thiopurines |
20% (5/25)= clinical remission; 24% (6/25)= clinical response |
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Boschetti66. Boschetti G, Nancey S, Moussata D, Stefanescu C, Roblin X, Chauvenet M, Stroeymeyt K, Bouhnik Y, Flourie B. Tacrolimus induction followed by maintenance monotherapy is useful in selected patients with moderate-to-severe ulcerative colitis refractory to prior treatment. Dig Liv Dis. 2014;46:875-80.
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2014 |
France |
Moderate-to-severe colitis refractory to other treatments |
UC-DAI at 4 and 12 weeks |
30 |
Tacrolimus 0.1-0.2 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
steroids; thiopurines |
47% (14/30)= clinical remission; 70% (21/30)= clinical response in 4 weeks |
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Hiraoka1111. Hiraoka S, Kato J, Moritou Y, Takei D, Inokuchi T, Nakarai A, Takahasi S, Harada K, Okada H, Yamamoto K. The earliest trough concentrarionredicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients. BMC Gastroenterol. 2015;15:53.
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2015 |
Japan |
Colitis moderada-severa cortico-dependiente/refractaria |
Lichtiger score up to 2-3 weeks |
47 |
Tacrolimus 0.05-0.15 mg/kg/day (adjusted by serum target level: 10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
87% (41/47) showed remission and/or clinical response |
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Ikeya1414. Ikeya K, Sugimoto K, Kawasaki S, Iida T, Maruyama Y, Watanabe F, Hanai H. Tacrolimus for remission inductionn ulcerative colitis: Mayo endoscopic subscore 0 and 1 predicts long-term prognosis. Dig Liv Dis . 2015; 47:365-71.
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2015 |
Japan |
Moderate-to-severe colitis |
Colitis Activity Index. Mayo score for mucosal healing up to 12 weeks |
44 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
86.4% (38/44)= clinical response; 65.9% (29/44)= clinical remission; 43.8% mucosal healing |
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Kawakami1616. Kawakami K, Inoue T, Murano M, Narabayashi K, Nouda S, Ishida K, et al. Effects of oral tacrolimus s a rapid induction therapy in ulcerative colitis. World J Gastroenterol. 2015;21:1880-6.
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2015 |
Japan |
Steroid-dependent or refractory moderate-to-severe colitis |
Lichtiger score up to 4 weeks |
49 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
89.6%= clinical response; 75.6%= clinical remission in 4 weeks |
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Minami2020. Minami N, Yoshino T, Matsuura M, Koshikawa Y, Yamada S, Toyonaga T, Madian A, Honzawa Y, Nakase H. Tacrolimus or infliximab for severe ulcerative colitis: short-term and long-term data from a retrospective observational study. BMJ Open Gastro. 2015;2:e000021.
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2015 |
Japan |
Moderate-to-severe colitis refractory to other treatments |
Mayo score up to 8 weeks |
22 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
90.9% (20/22)= clinical response; 63.63% (14/22)= clinical remission in 8 weeks |
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Hiraoka1212. Hiraoka S, Inokuchi T, Takei D, Nakarai A, Sugihara Y, Morito Y, Takahashi S, Harada K, Okada H, Yamamoto K, Kato J. Tacrolimus therapy for outpatients with refractory ulcerative colitis. Gastroenterology. 2015;148:(Suppl 1):870-1.
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2015 |
Japan |
Moderate-to-severe colitis refractory to other treatments |
CAI |
24 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
79% (19/24)= remission and/or response |
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Endo99. Endo K, Onodera M, Shiga H, Kuroha M, Kimura T, Hiramoto K, Kakuta Y, Kinouch Y, Shimosegawa T. A comparison of short nd long-term therapeutic outcomes of infliximab - versus tacrolimus-based strategies for steroid-refractory ulcerative colitis. Gastroenterol Res Prac 2016;3162595.
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2016 |
Japan |
Steroid-dependent or refractory moderate-to-severe colitis |
CAI up to 8 weeks |
47 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
68.08% (32/47)= clinical response; 55.31% (26/47)= clinical remission. 14.89% (7/47)= colectomy on follow up |
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Yamamoto3333. Yamamoto T, Shimoyama T, Umegae S, Matsumoto K. Tacrolimus vs anti-tumor necrosis factor agents formoderately to severely active ulcerative colitis: a retrospective observational study. Aliment Pharmacol Ther . 2016;43:705-16.
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2016 |
Japan |
Steroid-dependent or refractory moderate-to-severe colitis |
UC-DAI up to 12 weeks |
50 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
62% (31/50) = clinical response; 40% (20/50)= clinical remission |
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Nuki2323. Nuki Y, Esaki M, Asano K, Maehata Y, Umeno J, Moriyama T, Nakamura S, Matsumoto T, Kitazono T. Comparison of the therapeutic efficacy and safety between tacrolimus and infliximab for moderate-to severe ulcerative colitis: a single center experience. Scand J Gastroenterol 2016;51:700-5.
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2016 |
Japan |
Moderate-to-severe colitis |
UC-DAI up to 10 weeks |
21 |
Tacrolimus 0.1 mg/kg/day (adjusted by serum target level:10-15 ng/mL) |
aminosalicilates; steroids; thiopurines |
85.7% (18/21)= clinical response; 66.7% (14/21)= clinical remission in 10 weeks |