Background: Resistant ulcerative proctitis can be extremely difficult to manage. Topically administered tacrolimus, however, may be effective in difficult-to-treat proctitis
Methods: This was randomized, double-blind, placebo-controlled induction trial of rectal tacrolimus in patients with active ulcerative colitis funded by the Broad Medical Research Program (Clinicaltrials.gov registration: NCT01418131). Eleven patients received rectal tacrolimus (0.5mg/ml), and 10 placebo, for 8 weeks. The primary endpoint was clinical response by using the Mayo clinic score.
Results: An interim analysis after 20 patients had completed the study demonstrated highly significant differences between the groups and the study was closed due to ethical considerations with patients already recruited allowed to complete the study. The primary endpoint was met in 8/11 (73%) patients receiving rectal tacrolimus and 1/10 patients receiving placebo (10%; p=0.004). Of the secondary endpoints, 5 (45%) rectal tacrolimus patients achieved clinical remission compared to none receiving placebo (p=0.015). Mucosal healing at week 8 was achieved in 8 (73%) patients receiving rectal tacrolimus compared to 1 (10%) receiving placebo (p=0.004). The IBDQ increased ≥16 points over baseline in 5 (45%) of the tacrolimus and 2 (20%) of the placebo patients (p=0.36). Finally, the average partial Mayo score was numerically lower in the tacrolimus-treated group compared to placebo at week 2 (4.3±0.74 vs. 5.8±0.64; p=0.15) and week 4 (3.7±0.96 vs. 5.8±0.6; p=0.08) but was significantly lower at week 8 (3.3±1.2 vs. 6.7±0.62; p=0.01). There were no safety issues identified with rectal tacrolimus use.
Conclusions: Rectal tacrolimus was more effective than placebo for induction of a clinical response, clinical remission and mucosal healing in resistant ulcerative proctitis