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

Abstract

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.

Oral Tacrolimus for Megacolon in Patients with Severe Ulcerative Colitis

“…In a prospective multicenter study, we found that rapid induction therapy with oral tacrolimus (started at a dose of 0.1 mg/kg daily without food) achieved a high trough level (10-15 ng/mL) in more than 90% of patients and significantly suppressed the CAI beginning two days after treatment (13). Therefore, the administration of top-down or accelerated step-up therapy with tacrolimus may improve the prognosis of refractory UC, similar to that observed with infliximab in patients with Crohn's disease (6). In Case 1, the patient had steroid-naive UC, and top-down therapy with tacrolimus resulted in a marked improvement.…”

“…Since calcineurin inhibitors have a rapid onset of action and are highly effective in patients with refractory UC, they are approved as alternative treatment agents for refractory UC under the national health insurance system in Japan (5). Since differences in the onset of action of various agents are thought to influence the achievement and maintenance of disease remission, early intervention with tacrolimus may improve the long-term prognosis of patients with UC (6). In this paper, we report two cases of severe UC with megacolon that were successfully treated with tacrolimus, including a steroid-naïve patient.…”

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

“…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.…”

Previous exposure to biologics and C-reactive protein are associated with the response to tacrolimus in inflammatory bowel disease

“…We can obtain more evidence, almost all from retrospective studies, demonstrating relatively good efficacy rates in UC and CD. In UC, retrospective studies have reported remission rates between 9.3-80%, which reflects the high variability between the study population, route of administration, mean drug blood levels and the criteria for evaluating response (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Remission rates demonstrated a similar variability ranging from 9.4-75% in clinical trials and prospective studies (1,2,(16)(17)(18)(19).…”

“…The drug was maintained for a median duration of 11 months (IQR [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Ten patients received the drug for at least 12 months.…”