Transdermal nicotine improved symptoms in ulcerative colitis
ACP J Club. 1994 July-Aug;121:17. doi:10.7326/ACPJC-1994-121-1-017
Pullan RD, Rhodes J, Ganesh S, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994 Mar 24;330:811-5.
To evaluate the effectiveness of transdermal nicotine, in addition to conventional maintenance therapy, in improving symptoms in patients with active ulcerative colitis.
Randomized, double-blind, placebo-controlled trial with 6 weeks of follow-up.
3 hospitals in the United Kingdom.
77 patients (mean age 44 y, 57% men) with left-sided ulcerative colitis who had relapsed. Exclusion criteria were enteric infection or other medical problems, pregnancy, lactation, change in maintenance anticolitis therapy during the past 4 weeks, or current smoking. 5 patients (6%) did not complete the study.
35 patients were allocated to receive transdermal nicotine patches with doses titrated from 5 or 25 mg of nicotine over a 16-hour period. 37 patients were allocated to receive placebo patches. All patients continued to take the same doses of the anticolitis drugs they had taken during the 4 weeks before study enrollment.
Main outcome measures
Remission, change in the global clinical grade of colitis and histologic grade, stool frequency, abdominal pain, fecal urgency, and side effects.
More patients in the nicotine group had complete remission than did patients in the placebo group (P = 0.03), and fewer patients reported mucus in stools (P = 0.002) (Table). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and in the histologic grade (P = 0.03), lower daily stool frequency (P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). 23 patients (66%) in the nicotine group had side effects compared with 11 patients (30%) in the placebo group (P = 0.002) (Table). The most common side effects in the nicotine group were nausea, light-headedness, headache, sleep disturbance, dizziness, skin irritation, sweating, vomiting, and tremor.
Transdermal nicotine, in addition to conventional maintenance therapy, improved the symptoms in patients with active ulcerative colitis.
Source of funding: In part, Kabi Pharmacia.
For article reprint: Dr. J. Rhodes, Department of Gastroenterology, Ward A7, University Hospital of Wales, Health Park, Cardiff, United Kingdom. FAX 44-222-743-821.
Table. Transdermal nicotine vs placebo for active ulcerative colitis*
|Outcomes at 6 wk||Nicotine||Placebo||RBI (95% CI)||NNT (CI)|
|Complete symptom relief||49%||24%||100% (6 to 291)||4 (2 to 52)|
|No stool mucus||57%||22%||164% (40 to 428)||3 (2 to 8)|
|RRI (CI)||NNH (CI)|
|Side effects||66%||30%||121% (31 to 292)||3 (2 to 8)|
*Abbreviations defined in Glossary; RBI, RRI, NNT, NNH, and CI calculated from data in article.
That cigarette smoking now seems beneficial in ulcerative colitis not only runs contrary to the past 25 years of the Surgeon General's position on tobacco but provides physicians with a new and amusing opportunity to ponder events at both ends of the alimentary tract.
Comparing transdermal nicotine with placebo, Pullan and colleagues observed remission in half the treated patients compared with one quarter of the placebo group. Side effects, occurring especially in nonsmokers, were a limitation of therapy; lowering the administered dose decreased nicotine symptoms. The optimal amount and route of delivery remain to be determined.
Nicotine, which forms the basis for this study, is a potent vasoconstrictor, but possesses selective vasodilatory properties in the mesenteric circulation. Proposed mechanisms of action include increased intestinal permeability, decreased prostaglandin production, and improved mucin production in the colon (1, 2).
Adventurous clinicians probably will feel most comfortable recommending nicotine to former smokers with colitis, less so to nonsmokers, and rarely to persons with vascular insufficiency or desperately ill persons with colitis. Pullan and colleagues do not suggest that cigarettes will replace corticosteroids, aminosalicylates, immunosuppressives, or hyperalimentation; however, by extending a clinical observation to a therapeutic finding, they have helped us understand more about this baffling illness. Treating an idiopathic disease with a drug whose action is obscure is only slightly less common in 1994 than it was in 1794.
Pending the receipt of contradictory data, adjunctive treatment of ulcerative colitis might well include nicotine.
I. David Shocket, MD
David A. Morowitz, MDWashington Hospital CenterWashington, D.C., USA