A Randomized Trial of Nicotine Enemas for Active Ulcerative Colitis

Ingram, John R.; Thomas, G. A. O.; Rhodes, J.; Green, John T.; Hawkes, Neil; Swift, Jill; Srivastava, E. D.; Evans, Bruce; Williams, Geraint T.; Newcombe, Robert G.; Courtney, Edward; Pillai, Suresh

doi:10.1016/s1542-3565(05)00849-9

Cited by 68 publications

(47 citation statements)

References 26 publications

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“…20 What is severely limiting to the potential use of nicotine as treatment in UC is the high frequency of adverse events when compared to conventional therapy. Of the three RCTs examining nicotine vs. placebo in induction of remission 77,78,85 the RR of an adverse event occurring in the nicotine group was found to be 1.95 (95% CI: 1.38-2.78) and the RR of withdrawal due to an adverse event 3.44 (95% CI: 0.71-16.71). 3 The two RCTs comparing nicotine and oral corticosteroid treatments 80,82 similarly found the RR of withdrawal due to adverse events to be 2.28 (95% CI: 0.76-6.83).…”

Section: Discussionmentioning

confidence: 98%

“…A RCT 85 of active distal UC randomised 104 patients to either 6 mg nicotine enemas or placebo, whilst continuing on their regular medication regimen. Remission or improvement in disease was measured by clinical, sigmoidoscopic and histological means at 4 weeks.…”

mentioning

confidence: 99%

“…Only 27% of the treatment group achieved remission, compared with 33% of the placebo group (P = 0.55). 85 Ingram et al 85 concluded that, although well tolerated, 6 mg nicotine enemas were not clinically efficacious in inducing remission of UC.…”

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confidence: 99%

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Review article: ulcerative colitis, smoking and nicotine therapy

Lunney

Leong

2012

Aliment Pharmacol Ther

119

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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.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

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Review article: ulcerative colitis, smoking and nicotine therapy

Lunney

Leong

2012

Aliment Pharmacol Ther

119

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“…[78][79][80] Most likely nicotine side effects, due to interaction with all nAChR subtypes, prevent effective dosing in patients. In view of the side effects, more 'specific' α7nAChR agonists have been developed.…”

Section: Inflammatory Bowel Diseasementioning

confidence: 99%

The vagal innervation of the gut and immune homeostasis

Matteoli

Gomez‐Pinilla

Giovangiulio

et al. 2015

Autonomic Neuroscience

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The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.

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“…All were non-smokers and 16 of 17 improved their St Mark's score, stool frequency and urgency improved in 12 patients and the endoscopic and histological scores improved in 10 [72] . The only randomized placebo-controlled study that investigated the use of 6 mg nicotine enemas for 6 wk in 104 patients with active UC, however, demonstrated no significant benefit with nicotine over placebo enemas with clinical remission achieved in 27% patients on active treatment and 33% on placebo [73] .…”

Section: Nicotine Enemasmentioning

confidence: 99%

Novel topical therapies for distal colitis

Lawrance¹

2010

WJGPT

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Distal colitis (DC) can be effectively treated with topical 5ASA agents. Suppositories target the rectum while enemas can reliably reach the splenic flexure. Used in combination with oral 5ASAs, the control of the inflamm ation is even more effective. Unfortunately, resistant DC does occur and can be extremely challenging to manage. In these patients, the use of steroids, immu nosuppressants and the antitumor necrosis factor α agents are often required. These, however, can be associated with systemic side effects and are not always effective. The investigation of new topical therapeutic agents is thus required as they are rarely associated with significant blood drug levels and side effects are infrequent. Some of the agents that have been proposed for use in resistant distal colitis include butyrate, cycl osporine and nicotine enemas as well as tacrolimus suppositories and tacrolimus, ecabet sodium, arsenic, lidocaine, rebamipide and Ridogrel ® enemas. Some of these agents have demonstrated impressive results but the majority of the agents have only been assessed in small openlabelled patient cohorts. Further work is thus required with the investigation of promising agents in the context of randomized doubleblinded placebo controlled trials. This review aims to highlight those potentially ef fective therapies in the management of resistant distal colitis and to promote interest in furthering their investi gation.

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A Randomized Trial of Nicotine Enemas for Active Ulcerative Colitis

Cited by 68 publications

References 26 publications

Review article: ulcerative colitis, smoking and nicotine therapy

Review article: ulcerative colitis, smoking and nicotine therapy

The vagal innervation of the gut and immune homeostasis

Novel topical therapies for distal colitis

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