Rescue therapy with tacrolimus is effective in patients with severe and refractory inflammatory bowel disease

Abstract

Summary Background : Oral tacrolimus, approved for the prophylaxis of organ rejection in liver or kidney transplants, has been reported to be effective in anecdotal cases of refractory inflammatory bowel disease. Aim : To evaluate the usefulness of low‐dose oral tacrolimus in refractory inflammatory bowel disease. Methods: Thirty‐one adult Caucasian patients with steroid‐dependent (n = 15) or steroid‐refractory (n = 16) inflammatory bowel disease (Crohn's disease, n = 6; ulcerative colitis, n = 23; pouchitis, n = 2) were enrolled. Tacrolimus (0.1 mg/kg body weight per day) was administered orally in 30 patients and initially intravenously in one patient (0.01 mg/kg body weight per day), aiming for serum trough levels of 4–6 ng/mL. The median treatment duration was 12 months (range, 1–137 months). Results : Twenty‐eight patients (90.3%) experienced a clinical and laboratory response and 20 (64.5%) went into remission. One ulcerative colitis patient and two Crohn's disease patients did not improve. Three ulcerative colitis patients (9.7%) were colectomized at 1, 12 and 24 months after tacrolimus initiation. In 19 of 23 patients (82.6%) taking steroids, steroids were reduced or discontinued. Side‐effects included a temporary rise of creatinine (n = 3, 9.7%), tremor or paraesthesias (n = 3, 9.7%), hyperkalaemia (n = 1, 3.2%), hypertension (n = 1, 3.2%) and an opportunistic infection (n = 1, 3.2%). Conclusion : Oral tacrolimus is safe and effective in refractory inflammatory bowel disease.

Efficacy of Rectal Tacrolimus for Induction Therapy in Patients With Resistant Ulcerative Proctitis

“…there are numerous open-labelled studies in both UC and CD that suggest efficacy in the short-term, and with promising long-term data [13][14][15][16][17][18] . The evidence would suggest, however, that the blood trough levels should be at least 10ug/L in order to achieve the best efficacy (therapeutic range 5-20ug/L), but the higher the trough level the more likely a patient will suffer an adverse effect 19 .…”

Escherichia coli Strain Nissle 1917 Ameliorates Experimental Colitis via Toll-Like Receptor 2- and Toll-Like Receptor 4-Dependent Pathways

“…Mucosal inflammation is initiated and perpetuated by the secretion of proinflammatory and chemotactic cytokines, and potent anti-inflammatory drugs are able to inhibit their release (3,4). E. coli Nissle 1917 given orally or rectally to wt mice, significantly reduced the secretion of the proinflammatory antigen-specific T helper type 1 (Th1)-derived cytokines TNF-␣ and IFN-␥, as well as the chemokine MCP-1.…”

Induction of Remission and Maintenance Therapy with Tacrolimus in Refractory Ulcerative Colitis with Adverse Events from 5-ASA and Thiopurine

“…The second relapse was severe both clinically and endoscopically. Therefore, TAC add-on therapy was used for the steroid-dependent refractory UC [4,5].…”