A randomized trial of nicotine enemas for active ulcerative colitis.

BACKGROUND & AIMS: Ulcerative colitis (UC) is largely a disease of nonsmokers in which transdermal nicotine improves the symptoms but often causes adverse events (AEs). Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC. METHODS: We treated 104 patients with active UC with either 6-mg nicotine enemas or placebo enemas for 6 weeks in a randomized double-blind study. Patients continued their oral therapy, if any, for UC: 68 patients were taking mesalamine, 15 patients were taking prednisolone, and 12 patients were taking thiopurines during the study. Clinical, sigmoidoscopic, and histologic assessments were made at baseline and at the end of the study and symptoms were recorded daily on a diary card. The primary end point was induction of clinical remission and clinical improvement also was measured by the UC disease activity index. After the study, patients then used nicotine enemas daily for 4 weeks and sigmoidoscopy with a biopsy examination was repeated. AEs and salivary cotinine levels were monitored throughout the study. RESULTS: Clinical remission was achieved in 14 of 52 (27%) patients on active treatment and 14 of 43 (33%) patients on placebo (P = .55). The UC disease activity index improved by 1.45 points in the active group and by 1.65 points for those on placebo (P = .88). Only 1 patient discontinued treatment because of an AE (abdominal pain). In the 47 patients taking mesalamine only, active treatment conferred benefit that was not statistically significant; disease remission occurred in 9 of 25 patients on active therapy and 4 of 21 patients on placebo (P = .20). CONCLUSIONS: Six-milligram nicotine enemas were well tolerated but were not found to be efficacious for active UC.

Preliminary observations of oral nicotine therapy for inflammatory bowel disease: an open-label phase I-II study of tolerance.

BACKGROUND: Transdermal nicotine provides benefit in active ulcerative colitis but is often associated with adverse events (AEs). An oral formulation has been developed to minimize AEs. This study was undertaken to make initial observations on the safety and tolerance of oral nicotine therapy in inflammatory bowel disease; the effect on disease activity was also noted. METHODS: Twenty-six patients with ulcerative colitis, 11 with active disease, and 5 patients with Crohn's colitis (2 with active disease) were given oral nicotine in 3-mg capsules, gradually increasing the dose to the maximum tolerated. AEs were recorded, concomitant prednisolone and/or azathioprine were reduced where possible, and disease activity was reassessed at the end of nicotine treatment. RESULTS: Patients were followed for up to 12 months. Twenty-nine of 31 could tolerate at least 6 mg of nicotine each day, and 5 patients tolerated at least 18 mg daily. Twenty-four patients had nicotine-related nonserious AEs; over one half occurred during the period of dose escalation, but 7 discontinued treatment because of them. Six of the 13 patients with active disease became asymptomatic, whereas 3 patients in remission developed active symptoms; 11 patients reduced their concomitant medication. CONCLUSIONS: Oral nicotine is a safe potential treatment of inflammatory bowel disease, but there is considerable variation in tolerance.