Transcript Barts and The London Presentation

Effects of a combination of
varenicline and nicotine patch
on post-quitting urges to
smoke
Katie Myers Smith BSc MSc CPsychol
Research Fellow
Wolfson Institute of Preventive Medicine
Queen Mary University of London
Disclosures
•
The study was supported by an investigatorinitiated grant from Pfizer, who also supplied
varenicline. Nicotine and placebo patches were
supplied by McNeil.
•
The two pharmaceutical companies had no
involvement in the design and conduct of the
study, analysis and interpretation of the data, or
preparation of the manuscript.
Evidence that patch + a rapid
delivery form of NRT more
effective than single NRT use1
Current pharmacotherapy for
smoking cessation
Combination of NRT
recommended by The National
Institute for Health and Clinical
Excellence (NICE)2
•Nicotine Replacement Therapy (NRT)
• Insufficient evidence that
bupropion + NRT increases
long term abstinence3
• Combination not
recommended by NICE2
Patch, gum, lozenge, inhaler, nasal spray, minis,
mouth spray
•Bupropion ?
•Varenicline
1. Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation.
Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD000146. DOI: 10.1002/14651858.C
D000146.pub3
2. www.nice.org.uk/nicemedia/pdf/PH010guidance.pdf
3. Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database of
Systematic Reviews 2007, Issue 1. Art. No.: CD000031. DOI: 10.1002/14651858.CD000031.pub3.
Combining NRT & varenicline:
does it make sense?
• Both act on nAChRs (full and partial agonist)
• Both medications seem to achieve their effect on abstinence by
alleviating the discomfort of nicotine withdrawal [1,2].
• It is not clear if the central effects of the two medications are
sufficiently different to allow synergy, but if they do differ, their
combination could have some beneficial effects.
1. Stead LF, Perera R, Bullen C, Mant D, Lancaster T: Nicotine replacement therapy for smoking
cessation. Cochrane Database Syst Rev 2008, 1, CD000146.
2. Cahill K, Stead LF, Lancaster T: Nicotine receptor partial agonists for smoking cessation.
Cochrane Database Syst Rev 2011, 2, CD006103.
Ebbert et al (2009)
• Observational cohort study
Setting – inpatient smoking cessation facility
Medications – NRT with/without varenicline, NRT
with/without bupropion
Results – no difference in outcome, no safety
issues reported with combination treatment
• Currently no RCTs looking at varenicline+ NRT
Why it is important to do this
research
• Increased number of dependent smokers
• Anecdotal clinical experience of benefit but
needs to be experimentally investigated.
Study Aims
To examine if there are differences between
varenicline + nicotine patches
varenicline + placebo patches
In reduction of urges to smoke and withdrawal
relief at 24hr and 1 week after quitting (primary
endpoint)
In short term abstinence rates (secondary
endpoint)
Flow of participants
Potential participants
responding to adverts
(n=514)
Not invited to screening (n=234)
- Not meeting inclusion criteria
(n=72)
- Did not want to participate
(n=162)
Invited to
screening/consent
session (n=280)
Varenicline
use for 12
weeks
Attended
screening/consent
session (n=144)
Not eligible (n=10)
Randomised at TQD
(n=117)
Did not attend randomisation
session (n=17)
Allocated to placebo
patch (n=59)
Allocated to nicotine
patch (n=58)
Completed follow-up
at 12-weeks post TQD
(n=31)
Completed follow up at
12-weeks post TQD
(n=33)
Patch use for
4 weeks
Measures
• Rating of urges to smoke
and tobacco withdrawal
symptoms (MPSS)
• Smoking status
• CO in expired breath(Lost
to follow up = SMOKER)
• AEs recorded
Abstinence endpoints
• Self reported abstinence at 24 hour
phone call
• Continuous, validated abstinence
at 1 week
• Russell Standard (up to 5 lapses
allowed since TQD with validated
report of no smoking at week 4) at
4 weeks post TQD
• Self reported abstinence at 12
weeks
Effect of combination on
withdrawal
• No significant effect of combination
treatment on urge to smoke or other
withdrawal symptoms at 24 hour & 1 week
post TQD
Abstinence
Period after TQD
24 hours
Placebo
Patch
(n=59)
Nicotine
patch (n=58)
Pearson Chisquare; p
value
80% (n=47)
79% (n=46)
0.00; p = 0.96
1 week
N (%)
59% (n=35)
69% (n=40)
1.18; p = 0.28
4 weeks
N (%)
59% (n=35)
60% (n=35)
0.01; p = 0.91
12 week* N (%)
29% (n=31)
36% (n=33)
0.73; p = 0.39
*Self reported outcome
Adherence to medications
• There was no difference in adherence to
medication between the two study arms at
any time point.
• Adherence to the combination treatment
during the crucial first week post TQD was
high.
Adverse events
• No sig differences in ratings of nausea or any other AEs
reported between the two groups at any time point
• AEs reported by more that 5% of participants included;
- Abnormal dreams
- Headache
- Insomnia
Comments
• Adding nicotine patches to varenicline had no
beneficial or detrimental effect on urges to
smoke, withdrawal discomfort, abstinence rates,
or adverse effects profile.
• Limitations; short-term follow up, small sample
size
• Patch use vs oral NRT use –short acting NRT
(e.g. nasal spray) could be more effective. These
products are typically under used as they require
more effort from users, which would in theory
reduce any benefit of combination treatment.
• Results from this study should be generalised to
short acting NRT with caution.
• No increase in nausea or any other AE was
seen.
• Results suggest that this combination is well
tolerated
Conclusion
• There is a widespread interest in combining NRT
and varenicline in the hope of improving
treatment outcomes.
• The results of this study suggest that such
practice may not be productive or economical.
Publication
• Hajek, P., Myers Smith, K., Dhani, A., &
McRobbie, H. (2013) Is a combination of
varenicline more effective in helping smokers
quit than varenicline alone? A randomised
controlled trial. BMC Medicine. 11; 140
• http://www.biomedcentral.com/17417015/11/140
Acknowledgments
• The study randomisation was conducted
by Mark Simmonds.
THANK YOU
[email protected]