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Transdermal Nicotine for Ulcerative Colitis


Ulcerative colitis has an incidence of 5-10 per 100,000 in the UK. For some time a lower incidence has been noticed in people who smoke cigarettes. A fine case-control study from Chicago put some figures on this, and the observation was followed by randomised trials where patients were treated with nicotine to allow us to establish causation and the magnitude of the effect.

Case-control study

One hundred patients with ulcerative colitis were matched for age and sex with community control subjects, and selected at random for a telephone interview to collect information on smoking habits, race, religion, income, occupation and education [1]. Smoking habits at the onset of symptoms were analysed using logistic regression.

Compared with those who had never smoked, current smokers were much less likely to have ulcerative colitis (odds ratio 0.13, 95% CI 0.05 to 0.38) - that is they were about eight times less likely to have ulcerative colitis. Former smokers' risk was no different from non-smokers.

Transdermal nicotine treatment

Two randomised studies have tried to answer the obvious question - does nicotine help in treating ulcerative colitis?

The first study [2], from the UK, randomised 72 patients with active ulcerative colitis between transdermal nicotine patches or placebo patches for six weeks and measured plasma nicotine and cotinine (a metabolite of nicotine). None of the patients currently smoked. The mean patch dose for those given transdermal nicotine patches was 17 mg/day (achieved by balancing adverse effects). For those given placebo patches, the mean daily "dose" was 19 mg ; the study was double-blind.

There were lots of outcome measures, including clinical symptom scoring, sigmoidoscopy and histology. The crude analysis showed that 17/35 patients (49%) given transdermal nicotine had complete symptomatic relief and a global clinical grade of 0 (1-3 bowel motions a day, formed, without blood or mucus, and with no constitutional symptoms) compared with 9/37 patients (24%) given placebo.

These findings have been largely confirmed by a US study [3]. Here 64 non-smoking patients with mildly to moderately active ulcerative colitis were randomised in a double-blind comparison of transdermal nicotine and placebo patches. The daily dose of nicotine was 11 mg for 1 week, increased up to 22 mg/day for three weeks.

The outcome was measured on a disease activity index which included scored for stool frequency, rectal bleeding, sigmoidoscopy findings, physician assessment and histology. A fall of three points on this scale was considered to be a clinical improvement. Such an improvement occurred in 12 of 31 patients (39%) receiving nicotine and 3 of 33 patients (9%) of those on placebo.

Bandolier is not wholly convinced that these two trials measured the same outcome, but if these results are combined the relative benefit of transdermal nicotine over placebo was 2.6 (1.4 to 4.6) and the number needed to treat (NNT) was 3.7 (2.4 to 8.4). This means that of four patients with active ulcerative colitis who are given transdermal nicotine at around 15 - 22 mg/day for four to six weeks, one will have symptom improvement who would not have done so with placebo.

Comment

All the patients continued with their normal treatments during these trials. There are only two placebo-controlled studies, with only 66 patients given transdermal nicotine, and the confidence interval around the NNT includes an NNT of 8 - only half as good as the point estimate NNT of 3.7.

There were adverse effects of various types. These were common, and some patients could not tolerate nicotine patches. In the first study 10 of 35 patients given nicotine dropped out, for instance, and one patient given nicotine in the second study had acute pancreatitis.

Two other studies in the UK were not so positive. One [4] was a randomised comparison of transdermal nicotine with oral prednisolone in active ulcerative colitis for 6 weeks. Although 6 of 19 (32%) patients given nicotine achieved full sigmoidoscopic remission, so did 14/24 patients (41%) given oral prednisolone. Another study which compared transdermal nicotine (15 mg for 16 hours daily) with placebo in 80 patients with ulcerative colitis in remission showed no difference in relapses between the groups [5].

So transdermal nicotine may help some patients, but is no miracle cure for active ulcerative colitis, nor does it stop relapses in those patients in remission.

References:


  1. MD Silverstein, BA Lashner, SB Hanauer. Cigarette smoking and ulcerative colitis: a case-control study. Mayo Clinic Proceedings 1994 69:425-9.
  2. RD Pullan, J Rhodes, S Ganesh et al. Transdermal nicotine for active ulcerative colitis. New England Journal of Medicine 1994 330:811-5.
  3. WJ Sandborn, WJ Tremaine, KP Offord et al. Transdermal nicotine for mildly to moderately active ulcerative colitis. Annals of Internal Medicine 1997 126:364-71.
  4. GAO Thamas, J Rhodes, K Ragunath et al. Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis. European Journal of Gastroenterology & Hepatology 1996 8:769-76.
  5. GAO Thamas, J Rhodes, V Mani et al. Transdermal nicotine as maintenance therapy for ulcerative colitis. New England Journal of Medicine 1995 332:988-92.



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