Transdermal Nicotine as Maintenance Therapy for Ulcerative Colitis

Background Since transdermal nicotine is of value in the treatment of active ulcerative colitis but is often associated with side‐effects, an alternative in the form of topical therapy with nicotine enemas has been developed. Methods In an open study, 22 patients with active colitis, all non‐smokers, were asked to take a 100 mL enema containing 6 mg of nicotine every night for 4 weeks. Pre‐trial treatment using mesalazine (n=16), oral prednisolone (8), cyclosporin (1) and azathioprine (1) was kept constant for the month prior to assessment and during the study period. Symptoms, with stool frequency, were recorded on a diary card and an endoscopy was performed with rectal biopsy at the beginning of the study and after 4 weeks. Results Seventeen of the 22 patients completed 1 month of treatment. Mean duration of relapse was 29 weeks, range 3–94. Sixteen of 17 improved their St Mark's score. Urgency and stool frequency improved in 12 patients, sigmoidoscopic and histological scores in 10. Three patients had a full remission of symptoms with normal sigmoidoscopy. Six of 10 with a partial response continued with the enemas for a second month and five showed further improvement with full remission in two. The enema appeared effective when added to conventional treatment and produced few side‐effects. Conclusion Topical nicotine therapy for ulcerative colitis may have a place in future management, but controlled studies are needed.

Section: Introductionmentioning

confidence: 99%

Nicotine enemas for active ulcerative colitis—a pilot study

Green

Thomas

Rhodes

et al. 1997

“…3 Nicotine vs. placebo patch. Three randomised controlled trials (RCTs), Pullan et al, 77 Sandborn et al 78 and Thomas et al 79 examined transdermal nicotine therapy compared to a placebo patch. Pullan et al 77 conducted a randomised, double-blind study in which 72 patients with active UC were treated with either nicotine patch or a placebo patch for 6 weeks.…”

Section: Clinical Studiesmentioning

confidence: 99%

Review article: ulcerative colitis, smoking and nicotine therapy

Lunney

Leong

2012

121

SummaryBackgroundSmoking is the best‐characterised environmental association of ulcerative colitis (UC). Smoking has been observed to exert protective effects on both the development and progression of UC.AimsTo examine the association between UC and smoking, possible pathogenic mechanisms and the potential of nicotine as a therapeutic agent in the treatment of UC.MethodsA literature search was conducted through MEDLINE, using the MeSH search terms ‘ulcerative colitis’ and ‘smoking’ or ‘nicotine’. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles.ResultsUlcerative colitis is less prevalent in smokers. Current smokers with a prior diagnosis of UC are more likely to exhibit milder disease than ex‐smokers and nonsmokers. There is conflicting evidence for smokers having reduced rates of hospitalisation, colectomy and need for oral corticosteroids and immunosuppressants to manage their disease. Multiple potential active mediators in smoke may be responsible for these clinical effects, including nicotine and carbon monoxide, but the precise mechanism remains unknown. Nicotine has demonstrated variable efficacy in the induction of remission in UC when compared to placebo and conventional medicines. Despite this, the high frequency of adverse events limits its clinical significance.ConclusionsNicotine's application as a therapeutic treatment in ulcerative colitis is limited. Presently, it may be an option considered only in selected cases of acute ulcerative colitis refractory to conventional treatment options. This review also questions whether nicotine is the active component of smoking that modifies risk and inflammation in ulcerative colitis.

“…10 The negative Thomas study of the 15 mg patch/16 h reported that the respective mean week 26 trough plasma nicotine and cotinine concentrations were 5.3 ng/mL and 62 ng/mL. 12 Thus, in patients with ulcerative colitis treated with transdermal nicotine, higher serum or plasma nicotine concentrations are associated with a therapeutic effect. This is in contrast to patients treated with nicotine tartrate liquid enemas in whom the therapeutic effect is apparently unrelated to the serum nicotine concentration.…”

Section: Discussionmentioning

confidence: 99%

“…11 In contrast, results from a controlled trial using a lower dose of transdermal nicotine (15 mg/16 h) for ulcerative colitis remission maintenance were no different than placebo. 12 Side-effects from transdermal nicotine were frequently noted in the studies discussed above and included contact dermatitis, nausea, vomiting, headaches, sleep disturbance, diaphoresis, tremor and lightheadedness. 9±12 Thus, although nicotine appears to be of bene®t as a therapeutic agent for active ulcerative colitis, long-term transdermal nicotine treatment is likely to be limited by side-effects.…”

Section: Introductionmentioning

confidence: 98%

Nicotine tartrate liquid enemas for mildly to moderately active left‐sided ulcerative colitis unresponsive to first‐line therapy: a pilot study

Sandborn

Tremaine

Leighton

et al. 1997

Ulcerative colitis is primarily a disease of non-smokers. 1±3 Two-thirds of ex-smokers with ulcerative colitis SUMMARY Background: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine as a liquid rectal enema results in less systemic nicotine absorption. Aim: To determine the safety and clinical response of nicotine tartrate liquid enemas for active left-side ulcerative colitis in a pilot study. Methods: Ten non-smoking patients with mildly to moderately active left-sided ulcerative colitis unresponsive to ®rst-line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively. Results: After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per