*Harry Perkins Institute of Medical Research, School of Medicine and Pharmacology, University of Western Australia, Murdoch, WA, Australia‡Centre for Inflammatory Bowel Diseases, Saint John of God Hospital, Subiaco, WA, Australia§IBD Research Group, QIMR Berghofer Medical Research Institute, University of Queensland School of Medicine, Brisbane, Queensland, Australia∥Department of Gastroenterology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia¶Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA, Australia#University of Adelaide, School of Medicine, SA, Australia**Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, NSW, Australia‡‡South Western Sydney Clinical School, University of NSW Medicine, Sydney, NSW, Australia§§Ingham Institute for Applied Medical Research, South Western Sydney Clinical School, UNSW Australia, Sydney, NSW, Australia
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Background & AimsResistant ulcerative proctitis can be extremely difficult to manage. Topically administered tacrolimus, however, may be effective in difficult-to-treat proctitis. This was a randomized, double-blind, placebo-controlled induction trial of rectal tacrolimus in patients with active ulcerative colitis.MethodsEleven patients received rectal tacrolimus (0.5 mg/mL), and 10 placebo, for 8 weeks. The primary endpoint was clinical response by using the Mayo Clinic score.ResultsA planned interim analysis after 20 patients had completed the study demonstrated highly significant differences between the groups and the study was closed because of ethical considerations with patients already recruited allowed to complete the study. The primary endpoint was met in 8 of 11 patients receiving rectal tacrolimus and 1 of 10 patients receiving placebo (73% vs 10%; P = .004). Of the secondary endpoints, 5 patients with rectal tacrolimus achieved clinical remission compared with none receiving placebo (45% vs 0%; P = .015). Mucosal healing at Week 8 was achieved in 8 patients receiving rectal tacrolimus compared with 1 (73% vs 10%) receiving placebo (P = .004). The Inflammatory Bowel Disease Questionnaire increased ≥16 points over baseline in 5 of the tacrolimus and 2 (45% vs 20%) of the placebo patients (P = .36). Finally, the average partial Mayo score was numerically lower in the tacrolimus-treated group compared with placebo at Week 2 (4.3 ± 0.74 vs 5.8 ± 0.64; P = .15) and Week 4 (3.7 ± 0.96 vs 5.8 ± 0.6; P = .08) but was significantly lower at Week 8 (3.3 ± 1.2 vs 6.7 ± 0.62; P = .01). There were no safety issues identified with rectal tacrolimus use.ConclusionsRectal tacrolimus was more effective than placebo for induction of a clinical response, clinical remission, and mucosal healing in resistant ulcerative proctitis (Clinicaltrials.gov registration: NCT01418131).