Rectal tacrolimus beat placebo at inducing clinical response, clinical remission and mucosal healing in patients with resistant ulcerative proctitis in a double-blind randomized controlled trial.
Further, the study was terminated early after the interim analysis revealed a significant treatment effect compared with placebo across multiple endpoints.
This study “identifies an effective new therapy for the induction of response, and remission, in patients with active distal UC that is resistant to topical and oral therapies,” Ian C. Lawrance, MD, of the Center for Inflammatory Bowel Diseases at Saint John of God Hospital, and the University of Western Australia, and colleagues wrote.
Tacrolimus, like cyclosporin, is a classical calcineurin inhibitor used as an immunosuppressive medication that has shown promise in UC, and it appears to act locally within the intestinal mucosa rather than systemically.
To further explore the encouraging results seen in prior studies, the researchers randomly assigned 11 adults with active UC to receive a rectal tacrolimus ointment (0.5 mg/mL), and 10 to receive placebo for 8 weeks. All patients had failed or were intolerant to conventional therapies.
The planned interim analysis after 20 patients completed the study showed “highly significant differences” between groups, with 73% of the treatment group vs. 10% of the placebo group achieving the primary endpoint of clinical response (P = .004).
Additionally, 45% vs. 0% achieved clinical remission (P = .015) and 73% vs. 10% experienced mucosal healing (P = .004). The tacrolimus group showed numerically lower partial Mayo scores at week 2, which became significantly lower at week 8 (P = .01).
Also, while not significantly different, 45% vs. 20% experienced at least a 16-point increase in IBD Questionnaire scores.
Finally, the researchers observed no safety issues related to tacrolimus.
Lawrance and colleagues noted that the data have yet to show the long-term safety and effectiveness of rectal tacrolimus, and the effectiveness of higher doses,. Further studies in resistant pouchitis and perianal Crohn’s disease are planned, they wrote.
They concluded that “rectal tacrolimus is effective for the induction of response, and remission, for patients with active distal UC that has been resistant to topical and oral therapies.” – by Adam Leitenberger
Disclosures: The researchers report no relevant financial disclosures.