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Efficacy of Zyban and NRT

Zyban launch - great for smokers but beware the hype

In its press release Glaxo makes the following claim: A large comparative study published in the NewEngland Journal of Medicine found that almostone in three people (30.3%) treated with Zyban were not smoking at one year,compared to 16.4% of people using a nicotine patch.  Zyban was thereby found to be almost twice as effective as anicotine patch in helping people to quit smoking and remain abstinent at theone year follow up. ASH believes this is a carefully worded and truestatement, but an incomplete and misleading summary of the evidence.  This information sheet explains gives dataon the efficacy of Zyban (bupropion) explains why many experts do not yetbelieve it is appropriate to describe Zyban as twice as effective as NRT.

There are two published studies on Zyban:

1. Hurt et al.A comparison of sustained releasebupropion and placebo for smoking cessation. New England Journal of Medicine1997; 337 (1195-1202.)

www.nejm.org/content/1997/0337/0017/1195.asp

This study of 615 (non-depressed) smokers showed 23.1%patients treated with Zyban were not smoking at one year, compared to 12.4%with placebo.

2. Jorenby et al.A controlled trial of sustained releasebupropion, a nicotine patch, or both for smoking cessation. New England Journalof Medicine 1999; 340 (685-691)

www.nejm.org/content/1999/0340/0009/0685.asp

This is the only study in which Zyban has been compareddirectly to NRT. This study of 893 smokers is the basis for claims that Zybanis twice as effective as NRT. This is based on the following results from thisstudy:

Not smoking at one year...

    Placebo = 15.6%.

    Nicotine patch = 16.4%

    Zyban = 30.3%

Given that 30.3% is nearly twice 16.4% - this has been usedto support the claim that Zyban is twice as effective as NRT.   The authors calculate 'odds ratios' of 1.1for nicotine patch and 2.3 for Zyban compared to placebo at one year - [seenote at end on 'odds ratios'].

Overall efficacy.  The figures aboveare for 'point abstinence' - the number not smoking at a point in time12 monthsafter the start of the trial. 'Continuous abstinence' - the number not smokingduring the 12 months - is also used as an indicator and this is generallyregarded as a more reliable indicator of the likely long term success oftreatment.  In the Jorenby et al study, the continuous abstinence figures are:

Not smoking during one year

    Placebo = 5.6%

    Nicotine patch = 9.8%

    Zyban = 18.4%

    Zyban + NRT combination = 22.5%

The first thing to note is that the quit rate by thismeasure is closer to one in five rather than one in three and that this mightbe a more realistic basis for claims. However, there should always be caution with using a single study tomake any generalised claim of efficacy - unpublished continuous abstinence datafrom the Hurt et al study suggests alower efficacy than Jorenby et al.

It should also be noted that the Jorenby et al study wasconducted in an intensive support setting - a smokers' clinic - and this may bedifferent to the conditions in which Zyban is used in the UK, where it will beprescribed by general practitioners.

Comparison with nicotine patches. On making the Zyban to NRT comparison, the efficacy by point abstinencedoes show twice the efficacy.  However,ASH believes it is premature and inappropriate to make this claim, given thecurrent state of the evidence - for the following reasons.

A. This is a single study and should be replicated beforedrawing any conclusions.

B. The result for the nicotine patch is very poor = only1.05 x placebo - odds ratio 1.1. Yet we know that NRT has a large evidence base(about 80 studies) suggesting that it is much more effective than this figurewould suggest. So the 'twice as effective' claim is based on an anomalousresult for the nicotine patch in a single study. Bupropion has only beencompared with, and combined with, one fixed dosage form of NRT - a patch. Theresult should not be generalised to administration forms intended for ad libuse.

C. The Cochrane collaboration undertakes systematic reviewsof evidence for the efficacy of smoking cessation treatments. According to theCochrane review, the odds ratio for continuous abstinence with NRT compared tocontrol was 1.72 (95% confidence interval 1.60 to 1.84), The odds ratios forthe different forms of NRT were 1.63 for gum, 1.77 for patches, 2.27 for nasalspray, 2.08 for inhaled nicotine and 1.73 for nicotine sublingual tablet. Forbupropion, the Cochrane review has pooled results of four studies (2 published)and given a combined odds ratio of 2.73. I shall resist translating thesefigures into a comparison of NRT and bupropion because.... www.update-software.com/cochrane/cochrane-frame.html

D. ... the Cochrane review (1999 issue 3, which issubscription only on CD) says of bupropion and nicotine replacement:"Nicotine replacement therapy (NRT) has proven efficacy in over 80 studies[...] and has a very benign side-effect profile. The early results for severalanti-depressants, especially bupropion, are sufficient to endorse their use inmedical practice. There is insufficient published evidence to recommendbupropion in preference to NRT or vice versa. Bupropion may also be helpful inthose who fail nicotine replacement." Cochrane is probably the'gold-standard' of evidence assessment.

E. This comparison question has also been evaluated by theUS FDA (Food and Drug Administration) and is reflected in the US prescriptioninformation for bupropion: "The comparisons between Zyban, NTS [NicotineTransdermal System] and combination treatment in this study [Jorenby et al] hasnot been replicated, and, therefore should not be interpreted as demonstratingthe superiority of any of the active treatment arms over any other."

On the basis of the analysis above, Clive Bates, Director ofASH said: 

"Zyban is an effectiveanti-smoking treatment, and that the first studies show very promising successrates. But until more studies have been done, it is too soon to be makingcomparisons between NRT and Zyban. Both products have an important role to playand will meet smokers' needs in different ways. The products may also be mosteffective when used in combination."

[Note on oddsratios; results and probabilities are sometimes expressed as 'odds', and comparisonsmade as 'odds ratios'. Roughly speaking, these work as follows... a 30%abstinence rate at 12 months means the odds of abstinence are 30:70 = 0.43. For15% success rate, the odds are 15:85 = 0.176. Dividing these gives odds ratio -2.4 in this example which is close to the bupropion result - this measure givesa more standardised comparison of treatment efficacy than comparing absolutesuccess rates and enables results from treatment in different settings.

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