Monday January 12 2015
The test measures how quickly the body metabolises nicotine
“A blood test could help people choose a stop-smoking strategy that would give them the best chance of quitting,” BBC News reports. The test measures how quickly an individual breaks down nicotine inside their body, which is known as the nicotine-metabolite ratio (NMR).
Researchers wanted to see whether people with “normal” and “slow” NMR responded differently to stop smoking treatments, and if the blood test could eventually be used as an aid to help guide people to the best treatments to help them quit smoking.
They first tested people and categorised them as slow or normal metabolisers of nicotine. These people were then randomised to an 11-week treatment plan of a placebo, nicotine patches or the stop smoking drug varenicline. All treatments were given in addition to behavioural counselling.
Overall, they found that varenicline was more effective at helping a “normal metaboliser” to quit than patches. For slower metabolisers, there was no difference in the effectiveness of the two treatments, but they tended to get more side effects with varenicline.
Importantly, quit rates were only different after the 11-week treatment. A significant proportion started smoking again six or 12 months later. Therefore, how to maintain quit rates in the longer term is an issue that needs to be resolved.
There are multiple methods available that can help you quit smoking. If one doesn’t work out for you, then you can always try another one.
Were did the story come from?
The study was carried out by researchers from the University of Pennsylvania and other institutions in the US and Canada. Funding was provided by the National Institutes of Health, Canadian Institutes of Health Research, Abramson Cancer Center, Centre for Addiction and Mental Health Foundation, and Pennsylvania Department of Health.
A number of the researchers had received grants from the pharmaceutical company Pfizer, which manufactures and sells varenicline. This arguably represents a conflict of interest (which was made clear in the study).
The study was published in the peer-reviewed medical journal The Lancet.
The UK media accurately reported the findings of the study.
What kind of research was this?
This was a randomised controlled trial aiming to see whether a new biological marker could help pick the most appropriate method of stopping smoking for someone.
The researchers say that there is considerable variability in a person’s treatment response and side effects to different treatments for tobacco dependence. This provides a strong incentive to try to find biomarkers that may indicate the optimal treatment for a particular individual. In this study, they identified a genetically-informed biomarker of nicotine clearance – the ratio of two breakdown products of nicotine (3ʹ-hydroxycotinine and cotinine). They referred to this as the nicotine-metabolite ratio (NMR).
In this study, people were assigned to placebo, nicotine patch or varenicline (all in addition to behavioural counselling) and they looked at how good the NMR was at predicting the response to each treatment.
What did the research involve?
The research included 1,246 smokers. They excluded people using e-cigarettes, taking other smoking treatments, with a history of substance misuse or other significant medical problems. At enrolment, all provided blood samples for testing of their NMR. Based on their NMR results, they were categorised as either “slow” or “normal” metabolisers of nicotine (based on a pre-defined cut-off level).
The smokers were randomised to three groups, stratified by their NMR status, to ensure they had an even number of slow and normal metabolisers in each group. All groups also received behavioural counselling. The participants were divided as such:
- placebo patch and placebo pill (408 people)
- nicotine patch and placebo pill (418 people)
- placebo patch and varenicline pill (420 people)
Treatment was given double-blind, with neither researchers nor investigators aware of treatment allocation or NMR status. The stop smoking treatment period lasted 11 weeks.
The main endpoint was seven-day point prevalence abstinence at 11 weeks, which was defined as no self-reported smoking (“not even a puff” as the study put it) for at least seven days before the telephone assessment, with in-person verification (by carbon monoxide levels). Participants lost to follow-up were considered smokers. Later follow-ups at six and 12 months were also conducted. The main aim was to compare the efficacy of a nicotine patch with varenicline by NMR group (normal metabolisers vs. low metabolisers).
What were the basic results?
At the end of the 11-week treatment, slow metabolisers had quit rates of 17.2% using a placebo, 27.7% using a nicotine patch and 30.4% using varenicline.
Normal metabolisers had quit rates of 18.6% using placebo, 22.5% using nicotine patch and 38.5% using varenicline.
From these results, varenicline was significantly more effective than the nicotine patch for normal metabolisers. Their odds of abstinence with varenicline were more than double that compared with the nicotine patch (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.38 to 3.42). Slow metabolisers were no more likely to achieve abstinence with varenicline than the nicotine patch (OR 1.13, 0.74 to 1.71).
Among normal metabolisers, the number of people needing to enter the stop smoking programme to achieve one case of abstinence (the number needed to treat or NNT) 11 weeks later was 26 using nicotine patches and just 4.9 with varenicline.
For slow metabolisers, the NNT was not much different: 10.3 for nicotine patch and 8.1 for varenicline.
The researchers also found that slow metabolisers were significantly more likely than normal metabolisers to have more severe side effects when taking varenicline compared to placebo.
How did the researchers interpret the results?
The researchers conclude that “Treating normal metabolisers with varenicline and slow metabolisers with nicotine patch could optimise quit rates while minimising side effects”.
This is a well-conducted randomised controlled trial, which found that use of the nicotine-metabolite ratio (NMR) may be helpful in indicating which stop smoking treatment may be best for different people. For those with a normal NMR, varenicline was more effective than a nicotine patch. For slower metabolisers, there was no significant difference in the effectiveness of the two treatments, but they tended to get more side effects with varenicline.
The study benefits from its large size, double-blind design and high follow-up rates.
However, there are still questions to be answered. For example, the difference in abstinence rates between varenicline and nicotine patch for normal metabolisers was significant at the end of 11-week treatment. But by six months, abstinence rates had generally deteriorated across all treatment groups and for both slow and normal metabolisers. Abstinence rates for normal metabolisers given varenicline were still significantly higher than those given nicotine patch at six months, but this difference was no longer significant at the 12-month follow-up.
How to maintain quit rates in the longer term after cessation of treatment still appears to be an issue that needs resolving, regardless of treatment or nicotine metabolism type.
Overall, the research is promising. Whether the NMR is something that will ever be brought into wider use when deciding on the most appropriate smoking cessation therapy is not currently known. Even if it is, other factors are also still likely to guide treatment decisions, such as individual preference or previously tried treatments.
What the study does highlight is that there are multiple methods available you can use to quit smoking. These range from nicotine replacement products such as patches or gum and medication such as varenicline and bupropion (Zyban). While currently unlicensed as a stop smoking treatment (and with little direct scientific evidence of their effectiveness), many people have found that e-cigarettes can help them quit or cut down smoking.
The important thing is not to get discouraged if your first attempt at quitting smoking is unsuccessful. Try a different method, as this could be better suited to you.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.