Effect of oral tacrolimus (FK 506) on steroid‐refractory moderate/severe ulcerative colitis

Högenauer, Christoph; Wenzl, H; Hinterleitner, Thomas; Petritsch, Wolfgang

doi:10.1046/j.1365-2036.2003.01662.x

Cited by 104 publications

(69 citation statements)

References 33 publications

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“…Glucocorticoid (GC) treatment can be effective on ulcerative colitis (UC) [1] , however, in relapsed cases, the conditions are frequently refractory even when a high dosage of GC is administered [2,3] . It is well known that a long-term use of GC often causes serious side effects [4] .…”

Section: Introductionmentioning

confidence: 99%

Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis

Ouyang²,

Wen³

et al. 2005

WJG

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AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GR and GR) may play an important role in it. This study was aimed to investigate the relationship between the expression of GR and GR in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS:Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n = 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GR and GR expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS:All cases were positive for GR and GR expression. Both positive association between GR expression and the response of UC to GC and strong negative association between GR expression and the response of UC to GC were identified. There was no significant association between GR/GR expression and the degree of inflammation of UC. CONCLUSION:These findings suggest that both GR and GR may play an important role in the action of GC, and that GR functions as a dominant negative inhibitor of GR. Expression of GR and GR in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.

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Section: Introductionmentioning

confidence: 99%

Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis

Ouyang²,

Wen³

et al. 2005

WJG

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“…Figure 1 shows the flow diagram which describes the reasons for citations exclusion. Finally, 22 studies (4)(5)(6)(9)(10)(11)(12)(13)(14)(15)(16)(17)(20)(21)(22)(23)(24)(25)28,30,32,33) that fulfilled eligibility criteria were included. Only two studies were randomized controlled trials (24,25) (Ogata 2006 and Ogata 2012); these were included for meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

“…It is worth mentioning, according to what is observed from uncontrolled studies, the relatively high proportion of patients who would eventually require colectomy in spite of receiving tacrolimus (4,5,10,13,28,32) (Fellermann 2002, Hogenauer 2003, Baumgart 2006, Benson 2007, Yamamoto 2008, Schmidt 2013. As a consequence, it would seem like tacrolimus could delay the need for colectomy in a selected group of patients -those moderate-to-severe UC patients with prior failure to other therapeutic alternatives.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Tacrolimus for Induction of Remission in Patients With Moderate-to-Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis

Lasa

Olivera

2017

Arq. Gastroenterol.

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-Background -There is evidence that shows that calcineurin inhibitors may be useful for the treatment of severe ulcerative colitis. However, evidence regarding the efficacy of tacrolimus for remission induction in this setting is scarce. Objective -To develop a systematic review on the existing evidence regarding the clinical efficacy of tacrolimus for the induction of remission in patients with moderate-to-severe ulcerative colitis. Methods -A literature search was undertaken from 1966 to August 2016 using MEDLINE, Embase, LILACS and the Cochrane Library. The following MeSH terms were used: "Inflammatory Bowel Diseases" or "Ulcerative Colitis" and "Calcineurin Inhibitors" or "Tacrolimus" or "FK506". Studies performed in adult ulcerative colitis patients that evaluated the clinical efficacy of tacrolimus for the induction of remission were considered for revision. A meta-analysis was performed with those included studies that were also placebo-controlled and randomized. Clinical response as well as clinical remission and mucosal healing were evaluated. Results -Overall, 755 references were identified, from which 22 studies were finally included. Only two of them were randomized, placebo-controlled trials. A total of 172 patients were evaluated. A significantly lower risk of failure in clinical response was found for tacrolimus versus placebo ]; moreover, a lower risk of failure in the induction of remission was also found versus placebo ]. Conclusion -Tacrolimus seems to be a valid therapeutic alternative for the induction of remission in patients with moderate-to-severe ulcerative colitis. HEADINGS -Inflammatory bowel diseases. Tacrolimus. Calcineurin inhibitors.

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“…Thus far, several uncontrolled (9,14,15,17,19) and two placebo-controlled studies (13,18) have demonstrated that tacrolimus can induce remission in both adults (9, 13-15, 17, 18) and children (19). Another calcineurin inhibitor, CsA, is also highly active (60% to 80%) in patients with UC whose disease fails to respond to intravenous corticosteroid therapy (20).…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Oral Tacrolimus in Patients with Moderate/Severe Ulcerative Colitis not Receiving Concomitant Corticosteroid Therapy

et al. 2013

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Objective The calcineurin inhibitor tacrolimus has been shown to be safe and effective as salvage therapy for steroid-refractory ulcerative colitis (UC). Since differences in the onset of action between various agents are thought to influence the achievement and maintenance of disease remission, top-down or accelerated stepup therapy with tacrolimus may be useful. However, the efficacy of tacrolimus in moderate to severe UC patients not receiving concomitant steroids remains unknown. Methods Ten patients (11 attacks) with active, moderate to severe UC were treated with oral tacrolimus at a dose of 0.1 mg/kg body weight daily. The dosages were adapted to maintain trough whole-blood levels of 10 to 15 ng/mL to induce remission and 5 to 10 ng/mL to maintain remission. Lichtiger scores, the incidence of adverse effects (serum creatinine and glucose) and long-term outcomes were assessed. Results At four weeks after the initiation of tacrolimus therapy, clinical remissions were observed for eight attacks (72.7%) and clinical responses were demonstrated for three attacks. At 12 weeks after the initiation of tacrolimus treatment, clinical remissions were achieved for nine attacks (90%). After a mean follow-up of 10.4 months, clinical remissions were maintained for eight of 11 attacks. During the tacrolimus treatment, the serum creatinine and glucose levels were not significantly elevated. Conclusion Oral tacrolimus is a safe and effective therapy for the treatment of moderate to severe UC in patients not receiving concomitant treatment with systemic steroids. Although further studies are required to establish the efficacy and safety of oral tacrolimus therapy in patients with UC, oral tacrolimus may represent a top-down or accelerated step-up treatment option for patients with moderate to severe UC.

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Effect of oral tacrolimus (FK 506) on steroid‐refractory moderate/severe ulcerative colitis

Cited by 104 publications

References 33 publications

Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis

Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis

Efficacy of Tacrolimus for Induction of Remission in Patients With Moderate-to-Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis

The Efficacy of Oral Tacrolimus in Patients with Moderate/Severe Ulcerative Colitis not Receiving Concomitant Corticosteroid Therapy

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