Transdermal nicotine for active ulcerative colitis. Outcome of ulcerative colitis after treatment with transdermal nicotine. Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial. Distal ulcerative colitis refractory to rectal mesalamine: role of transdermal nicotine versus oral mesalamine. Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis.
Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis.
                We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study.
                Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12).
                The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis. Transdermal nicotine appears to be of benefit in the short-term treatment of patients with ulcerative colitis. The aim of this study was to determine its long-term effects.
                A randomized, comparative study.
                Patients with mild to moderate clinical relapses of left-sided ulcerative colitis during maintenance treatment with mesalamine 1 g b.i.d. were allocated to an additional treatment with either transdermal nicotine or prednisone for 5 weeks. The first consecutive 15 patients per group, with clinical and endoscopic signs of remission, were followed up for 6 months, while continuing mesalamine maintenance treatment.
                Relapses of active colitis were observed in 20% of patients formerly treated with nicotine and in 60% of patients in the prednisone group (P = 0.027). Relapses occurred earlier in the latter group.
                Our results confirm that nicotine is useful in cases of ulcerative colitis with mild or moderate activity and suggest that remissions induced by nicotine may last longer than those obtained with oral corticosteroids. Ulcerative colitis is predominantly a disease of nonsmokers. Transdermal nicotine may help control clinical manifestations of this condition.
                To determine the efficacy of transdermal nicotine for controlling clinical disease activity in active ulcerative colitis.
                Randomized, double-blind, placebo-controlled, single-center clinical trial.
                Multispecialty group serving as an academic tertiary referral center.
                64 nonsmoking patients with mildly to moderately active ulcerative colitis despite the use of medication.
                Patients were stratified on the basis of smoking history, extent of disease, and concomitant medical therapy. After stratification, patients were randomly assigned to daily treatment with transdermal nicotine (n = 31) at the highest tolerated dose (11 mg for 1 week and then < or = 22 mg for 3 weeks) or placebo (n = 33).
                Clinical features were assessed at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Serum concentrations of nicotine were determined by using gas chromatography and mass spectrometry, and plasma concentrations of cotinine were measured by using high-performance liquid chromatography.
                At 4 weeks, 12 of 31 patients (39%) who received nicotine showed clinical improvement compared with 3 of 33 patients (9%) who received placebo (P = 0.007). Four patients receiving nicotine discontinued therapy because of side effects (contact dermatitis [n = 2], nausea [n = 1], and acute pancreatitis [n = 1]). At week 4, the nicotine group had a mean (+/-SD) trough serum nicotine concentration of 11.3 +/- 8.4 ng/mL and a mean trough plasma cotinine concentration of 192 +/- 95 ng/mL.
                Transdermal nicotine administered at the highest tolerated dosage (< or = 22 mg/d) for 4 weeks is efficacious for controlling clinical manifestations of mildly to moderately active ulcerative colitis. Distal ulcerative colitis usually responds to treatment with rectal mesalamine, but the management of refractory cases is poorly defined.
                To evaluate the possible therapeutic benefit of transdermal nicotine versus oral mesalamine.
                Thirty patients with left-sided ulcerative colitis unresponsive to treatment with a mesalamine 4 g enema at bedtime were randomly allocated to additional therapy with either transdermal nicotine 15 mg daily or oral mesalamine 800 mg tid for four weeks. Clinical remission was evaluated by Rachmilewitz's activity index and confirmed by sigmoidoscopy.
                Remission was observed in 12 of 15 patients receiving additional treatment with nicotine and in five of 15 patients receiving additional treatment with oral mesalamine (P=0.027).
                The addition of transdermal nicotine to treatment with mesalamine enemas is significantly superior to combined therapy with oral and rectal mesalamine in patients with distal ulcerative colitis refractory to rectal mesalamine alone. Ulcerative colitis is largely a disease of non-smokers. Previous controlled trials have shown benefit with transdermal nicotine when given with 5-aminosalicylic acid in active disease but not when given alone as maintenance therapy.
                To examine nicotine alone compared with prednisolone in active disease.
                Sixty-one patients with active ulcerative colitis were treated with either transdermal nicotine patches or 15 mg prednisolone for 6 weeks in a randomized, double-blind study. Incremental doses of nicotine were given for the first 9 days; patients tolerated between 15 and 25 mg daily. Most patients were taking mesalazine at entry which was discontinued at day 10; a few were taking topical steroids which were discontinued at the onset. Clinical, sigmoidoscopic and histological assessments were made at baseline and 6 weeks, or at premature withdrawal. Symptoms were recorded on a diary card, and the clinician made a global clinical assessment. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study.
                Forty-three patients completed the 6-week trial; of these, 6 of 19 in the nicotine group achieved full sigmoidoscopic remission compared with 14 of 24 with prednisolone (P = 0.08). In those who completed the 6-week study, there was significant improvement within both the nicotine and prednisolone group for the St Mark's score (P < 0.05 and P < 0.01, respectively), Global Clinical Grade (P < 0.01 for both), blood in the stool (P < 0.05 and P < 0.01), abdominal pain (P < 0.05 and P < 0.01) and sigmoidoscopic score (P < 0.01 and P < 0.001); differences between groups tend to favour prednisolone, but none reach statistical significance. However, on intention-to-treat analyses there is little clear evidence of improvement in either group apart from sigmoidoscopic score in which prednisolone was associated with a significantly greater improvement than nicotine (P < or = 0.05). The nicotine group had more withdrawals than the prednisolone group, 11 versus 7, respectively (P = 0.23), both for deterioration (6 vs. 5) and side effects (5 vs. 2, P = 0.15). Side effects were more frequently reported in the nicotine group (average 1.47 episodes per person) than the prednisolone group (average 0.61; P = 0.03), the most common of which were nausea, light-headedness and tremor.
                In those who managed to complete the 6-week study, nicotine alone appeared to be of only very modest benefit in acute colitis and was not as effective as 15 mg of prednisolone daily.
The results of this review provide evidence that transdermal nicotine is superior to placebo for the induction of remission in patient's with ulcerative colitis. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy. Adverse events associated with transdermal nicotine are significant and limit its use in some patients.