Effects of a combination of varenicline and nicotine patch on post-quitting urges to smoke

1. 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

2. The study was supported by an investigator-initiated 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. Disclosures

3. Evidence that patch + a rapid delivery form of NRT more effective than single NRT use1 Combination of NRT recommended by The National Institute for Health and Clinical Excellence (NICE)2 Current pharmacotherapy for smoking cessation • Nicotine Replacement Therapy (NRT) Patch, gum, lozenge, inhaler, nasal spray, minis, mouth spray • Bupropion • Varenicline • Insufficient evidence that bupropion + NRT increases long term abstinence3 • Combination not recommended by NICE2 ? 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.

4. 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. Combining NRT & varenicline: does it make sense? 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.

5. 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 Ebbert et al (2009)

6. Increased number of dependent smokers Anecdotal clinical experience of benefit but needs to be experimentally investigated. Why it is important to do this research

7. 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) Study Aims

8. Not invited to screening (n=234) - Not meeting inclusion criteria (n=72) - Did not want to participate (n=162) Flow of participants Potential participants responding to adverts (n=514) • Measures • Rating of urges to smoke and tobacco withdrawal symptoms (MPSS) • Smoking status • CO in expired breath(Lost to follow up = SMOKER) • AEs recorded Invited to screening/consent session (n=280) Attended screening/consent session (n=144) Not eligible (n=10) • 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 Did not attend randomisation session (n=17) Randomised at TQD (n=117) Allocated to nicotine patch (n=58) Varenicline use for 12 weeks Allocated to placebo patch (n=59) Patch use for 4 weeks Completed follow up at 12-weeks post TQD (n=33) Completed follow-up at 12-weeks post TQD (n=31)

9. No significant effect of combination treatment on urge to smoke or other withdrawal symptoms at 24 hour & 1 week post TQD Effect of combination on withdrawal

10. *Self reported outcome Abstinence

11. 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. Adherence to medications

12. No sig differences in ratings of nauseaor 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 Adverse events

13. 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 Comments

14. 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.

15. No increase in nausea or any other AE was seen. Results suggest that this combination is well tolerated

16. 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. Conclusion

17. 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/1741-7015/11/140 Publication

18. Acknowledgments • The study randomisation was conducted by Mark Simmonds.

19. THANK YOU Katie.smith@qmul.ac.uk