Patients with resistant ulcerative proctitis, a mild form of ulcerative colitis (UC), respond to therapy with rectal Prograf (tacrolimus) ointment, achieving clinical remission and mucosal healing, according to the results of a small clinical trial.
The study “Efficacy of Rectal Tacrolimus for Induction Therapy in Patients With Resistant Ulcerative Proctitis” was published in the journal Clinical Gastroenterology and Hepatology.
Approximately 25 percent of patients with UC have ulcerative proctitis, in which the inflammation is usually confined to the final segment of the large intestine, the rectum. Despite available therapies, patients can develop resistant ulcerative proctitis, meaning they do not respond to available therapies.
Prograf (tacrolimus) is a calcineurin inhibitor widely used as a topical immunosuppressive therapy with success in UC. Previous studies suggested that Prograf is a potential effective therapy for difficult-to-treat proctitis.
To expand and further confirm the results of these earlier studies, researchers performed a small Phase 4 clinical trial (NCT01418131) with a group of patients with active UC who failed to respond to previous therapies.
Patients were then assigned randomly to receive either a 0.5 mg/mL dose of a rectal Prograf ointment, twice a day, or a placebo (control) for 8 weeks. In total, 11 patients were assigned to the Prograf and 10 patients to the placebo arm of the study.
The study’s main outcome was to determine patients’ clinical response using the Mayo Clinic score. At baseline, the score was the same between patients randomized to Prograf or placebo group – ranging from 2 to 3.
The results showed that after 8 weeks 73 percent of patients treated with rectal Prograf achieved the study’s primary goal, but the same result was seen in only 10 percent of the patients on placebo. The mean Mayo score at Week 8 in the Prograf group was 4.5 and in the placebo group 8.8.
Moreover, “of the secondary endpoints, 5 of the patients receiving rectal tacrolimus achieved clinical remission whereas none of the patients receiving placebo achieved remission,” researchers wrote. This corresponds to 45 percent versus 0 percent in each group, respectively.
Healing of the intestinal mucosa also was achieved in eight patients treated with rectal Prograf, compared with one patient receiving placebo. Although it failed to reach statistical significance, the score of the Inflammatory Bowel Disease Questionnaire increased by more than 16 points over baseline in 45 percent of Prograf–treated patients versus 20 percent of those in the placebo group. This questionnaire assesses patients’ health-related quality of life.
Overall, these results show that “rectal tacrolimus was more effective than placebo for induction of a clinical response, clinical remission, and mucosal healing in resistant ulcerative proctitis,” the study concluded.