Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis.

BACKGROUND

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.

OBJECTIVE

To examine nicotine alone compared with prednisolone in active disease.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.