Simple water-based tacrolimus enemas for refractory proctitis

Background and Aims Rectal ulcerative colitis (UC) and Crohn's disease (CD) often do not respond to conventional therapies. Oral and suppository tacrolimus are effective but often poorly tolerated or are complex to formulate. Tacrolimus is topically active, water soluble, and has minimal systemic toxicity when administered rectally; we therefore tested a simple tap water-based enema formulation. Methods Tacrolimus powder from 1 mg capsules and tap water in a 60 mL syringe were delivered rectally. The primary end-point was endoscopic response (UC: MAYO score reduction by one point; CD: improvement in ulcer number and severity). Secondary end-points included endoscopic remission, clinical response, stool frequency, and rectal bleeding. Results Seventeen patients [12 UC, five CD, nine female, median age 31 years] with refractory rectal disease were treated. The majority of patients had failed immunosuppressive therapy [88% thiopurine; 71% biologic therapy]. Initial enemas included 1-4 mg tacrolimus daily and 1-3 mg tacrolimus maintenance three times a week for a median of 20 weeks (range 3-204). Concomitant thiopurine or biologic therapy continued. 94% tolerated therapy. Of 12 UC patients, eight (67%) achieved endoscopic remission, one further patient achieved endoscopic response, and median partial MAYO scores decreased (pre:4 vs. post:2; P = 0.010). Of five CD patients, three (60%) achieved endoscopic response, two (40%) endoscopic remission, and three (60%) clinical response. Stool frequency, rectal bleeding, and C-reactive protein levels improved. Strictures became endoscopically passable in all four affected patients. No major adverse events were reported, and four patients had disease flare. Conclusions Tacrolimus enemas are easy to prepare, well tolerated, effective, and safe. They should be included in the treatment armamentarium for inflammatory bowel disease-related refractory proctitis.