Tabex smoking drug shows promise

An anti-smoking drug called Tabex may “boost a person’s chances of ditching cigarettes three-fold,” The Sun has today reported.

The smoking cessation drug, also known as cytisine, has been available in some Eastern European and former Soviet countries, such as Russia, for more than 40 years. However, the researchers of this study said that the drug has not previously been tested in a way that would meet modern regulatory standards, which all drugs must satisfy before they can be marketed in the UK. To test the effectiveness of the drug, the researchers performed a study using 740 volunteers who were either given the drug or a dummy (placebo) drug for 25 days. They found that 12 months after treatment, 8.4% of participants taking cytisine had successfully quit, compared to 2.4% of participants taking the placebo. This equated to an extra 6% of people giving up smoking, a performance comparable to existing approved treatments.

As well as producing promising results, the drug is reported to be inexpensive, which singles it out as a potential future treatment within the UK. However, given that the trial was relatively small and short it is likely that more research will be needed to confirm its effectiveness and safety before regulators can approve its use.

The organisation that oversees drug licensing in the UK, the Medicines and Healthcare products Regulatory Agency (MHRA), says it has not recieved an application to license Tabex. The MHRA says: "Whilst we welcome new applications for promising medicines for use in the UK, it’s imperative that the product’s safety, quality and effectiveness is assessed to ensure the benefits outweigh the risks. It would be wrong to assume that the product has no known harmful side effect. All medicines have side effects – no effective medicine is without any risk."

Where did the story come from?

The study was carried out by researchers from University College London, the UK Centre for Tobacco Control Studies and the Cancer Centre and Institute of Oncology, Poland. It was funded by the UK’s National Prevention Research Initiative and published in the peer-reviewed New England Journal of Medicine . The trial itself was conducted at the smoking cessation clinic of the Maria Sklodowska-Curie Memorial Cancer Centre in Warsaw, Poland.

The news coverage of this story was mainly accurate. However, it should be noted that while cytisine has not been “banned” as one headline said, it does not have a licence to market in the UK.

What kind of research was this?

This was a randomised, double-blind placebo-controlled trial. The researchers said that cytisine has been available in Bulgaria since 1964 and is commercially available in countries such as Poland and Russia for approximately US $6-$15 per course of treatment. However, they said that despite the drug’s widespread use there have not yet been any large placebo-controlled trials that would adhere to modern regulatory standards. This study was performed to fulfil this requirement.

What did the research involve?

The researchers enrolled 740 individuals who smoked 10 or more cigarettes per day, and who were willing to attempt to stop smoking permanently. They were randomised to receive either cytisine or a placebo pill (370 in each group). The participants took cytisine or the placebo for 25 days, and were then assessed 6 and 12 months after the treatment period had ended to determine whether they had managed to give up smoking or if they had relapsed. The participants agreed prior to the trial not to take any other medications to stop smoking. Both groups received a minimal amount of counselling during the study.

During the 25-day treatment period, the participants followed a treatment schedule that has been licensed in several European countries, where the number of tablets taken decreased over time:

• 1-3 days: six 1.5mg tablets a day (one tablet every two hours)
• 4-12 days: five tablets a day for nine days
• 13-16 days: four tablets a day for four days
• 17-20 days: three tablets a day for four days
• 21-25 days: two tablets a day for five days

Participants were contacted 6 and 12 months after their treatment had ended and asked whether they had given up smoking. A “relapse” was defined as self-reported smoking of five or more cigarettes during the specified follow-up period (the previous 6 or 12 months). The carbon monoxide concentration in exhaled breath was measured for participants who reported that they had given up smoking, to confirm their reports.

The participants were also asked whether they had experienced any side-effects, and if so, to describe them. The researchers then coded the responses they received.

The researchers then analysed their results on the “intention-to-treat principle”, meaning that they analysed their results based on all the people that were originally randomised in the study, rather than just those they could contact. They considered treatment to have failed in any participants that they could not contact at the follow-up points.

What were the basic results?

Results after 12 months showed that 8.4% of the participants randomised to receive cytisine had not relapsed (in other words, had successfully quit smoking), compared to 2.4% of the participants randomised to receive placebo. This was a difference of 6% (95% CI 2.7% to 9.2%), which equated to people taking cytisine being 3.4 times more likely to give up than those taking a placebo (95% CI 1.7 to 7.1).

The researchers report that this increase in the rate of giving up smoking is higher than that reported for the existing drug vareniciline (smokers taking varenicline are 2.3 times more likely to quit than those taking a placebo) and nicotine-replacement therapy (1.6 times more likely). However, the absolute difference in rate (in this case 6%) was lower than that shown for vareniciline, and similar to that shown for nicotine-replacement therapy. Some differences may be due to the length of the treatment period: only 4 weeks in this trial but 8 weeks for nicotine-replacement therapy and 12 weeks for vareniciline.

Gastrointestinal (stomach and intestine) side effects, predominantly stomach-ache, dry mouth, dyspepsia and nausea, were reported significantly more frequently in participants receiving cytisine (13.8%) than those receiving placebo (8.1%). There were no other side effects, which were significantly more frequent in the group receiving cytisine. The two groups had similar rates of drug discontinuation and dose reduction.

Although this study only lasted 12 months and was not large enough for an assessment of uncommon adverse events, the researchers report that the latest Periodic Safety Update Report provided to the European Authorities, based on more than 7 million exposed persons, did not identify any safety signals: in other words, the drug is considered safe.

How did the researchers interpret the results?

The researchers said: “In this single-centre study, cytisine was more effective than placebo for smoking cessation. The lower price of cytisine, as compared with that of other pharmacotherapies for smoking cessation, make it an affordable treatment to advance smoking cessation globally.”

Conclusion

In this promising 12-month trial (involving a treatment period of 25 days), 8.4% of participants taking cytisine (brand name Tabex) managed to give up cigarettes, compared with 2.4% of participants taking placebo. This means that the participants taking cytisine were more than three times more likely to give up.

Although individuals in the group receiving cytisine experienced more gastrointestinal side-effects, the researchers said that other uncommon side effects are unlikely as this drug has been available in other countries for more than 40 years.

Other points to note are that:

• The trial was not large enough to assess the uncommon adverse events that could occur with the drug. Because the drug is in the same class as others linked to neuropsychiatric side effects and suicidal ideas, the researchers recommend continued surveillance of the 7 million people reported to be taking it.
• Compared to the therapies currently available in the UK, the number of extra people who are able to quit after taking cytisine is similar to those who can quit with nicotine-replacement therapy, although the course of treatment tested here is shorter. Specific research to compare it against treatments currently available in the UK may be warranted, along with studies of longer courses of the drug.
• In this study, the participants were given minimal behavioural support, such as counselling. The researchers suggest that combining cytisine with more intensive behavioural support could potentially increase the absolute quit rates.

Overall, this paper will generate discussion about how cytisine might fit into the range of treatments currently available, although more research is likely to be needed before the drug is approved.