1. P Tonnesen.2009 Smoking reduction Philip Tønnesen, M.D., Department of Pulmonary Medicine Copenhagen, Denmark

2. P Tonnesen.2009 Tobacco control Prevention Smoking cessation Smoking reduction

3. P Tonnesen.2009 Nicotine replacement 17 % of NRT is used for other than smoking cessation! i.e. 60 % use NRT < 2 weeks 40 % no instruction (GP or pharmacit) Temporary abstinence: during work, travel Smoking reduction

4. P Tonnesen.2009 Smokers Stops today 4% Wants to stop 29% Reduces now 17% Wants to reduce 16% Smokers in the Netherlands New smokers to reach with Reduction to Stop Happy smokers 34% Unhappy (ambivalent) smokers 66% 100% 80% 60% 40% 20% 0%

5. P Tonnesen.2009 Smoking Reduction Rationale 1.Aimed for smokers low in motivation to quit / unable to quit 2.Induction of permanent change in smoking habit 3.Compensation not 100% 4.Will not interfere with smoking cessation

6. P Tonnesen.2009 Smoking Reduction Cigarettes + NRT use Definition: arbitrary Cigarettes/day < 50 % of entry numbers plus any decrease in CO (1 ppm or >)

7. P Tonnesen.2009 Cessation-induction Ready to reduce smoking NRT increases reduction Self-efficacy increased Intention to quit increased Increased probability of a quit attempt Increased abstinence NRT prior to quitting decreases relapse Reducing prior to quitting decreases relapse

8. P Tonnesen.2009 Clinical Studies StudyMax trt time NRTSubjects Investigator(s) 96NNIN01618Inhaler400 Bolliger, Zellweger 98NNIN02712Inhaler429 Rennard, Glover, Muramoto 98NNCG01412Gum (2+4) 411 Tønnesen 980CHC-1013-02812Gum (4)364 Batra, Klingler 98NNCG01712Gum (2+4) 436 Woodbaker, Southcott, Saunders 980CHC-9021-00139Gum (2+4) 385 Haustein, Batra

9. P Tonnesen.2009 Gum and Inhalator Increase the Likelihood of Successful Sustained Reduction (2 Inhaler, 4 Gum studies) % Sustained Smoking Reduction From Week 6 (at least 50% reduction, verified by a lowered CO) * * * p<0.001 * *

10. P Tonnesen.2009 Gum and Inhalator Increase the Likelihood of Successful Cessation (2 Inhaler, 4 Gum studies) % Point Prevalence Cessation Rates (complete cessation, verified by a CO < 10 ppm) * * * * * p<0.001

11. P Tonnesen.2009 Smoking reduction Wennike, Tønnesen et al. Addiction 2003 411 smokers 24 cigarettes/day Motivation to reduce on 10-cm VAS: 9 Motivation to quit on 10-cm VAS: 5 Nicotine gum for up to 12 months

12. P Tonnesen.2009 Smoking reduction Wennike, Tønnesen et al. Addiction 2003 Reduction (sustained): ActivePlacebo 4-months14 %5 % (p<0.002) 1-year8.8 %1.5 % (p<0.001) 2-years6.3 %0.5 % (p<0.001)

13. P Tonnesen.2009 Smoking reduction Wennike, Tønnesen et al, Addiction 2003 Cessation (point): ActivePlacebo 4 months6.3 %0.5 % (p<0.001) 1-year11.2 %3.9 % (p<0.005) 2-years9.3 %3.4% (p<0.01)

14. P Tonnesen.2009 Motivation to quit

15. P Tonnesen.2009 Smoking cessation/reduction in COPD (Tønnesen et al.In press) 370 COPD patients Age :62 years FEV 1 : 1.57 (56 % predicted) Cigarettes/day: 20 FTND: 6.4 High – low support, NRT – placebo 12 weeks

16. P Tonnesen.2009 Smoking reduction in COPD NRT versus placebo: 6 months reduction rate: 21 % vs 15 % 12 months reduction rate:12 % vs 13 %

17. P Tonnesen.2009 Smoking cessation in COPD NRT versus placebo: 6 months quit rate: 23 % vs 10 % 12 months quit rate:17 % vs 10 % (OR 2.0)

18. P Tonnesen.2009 Reduction to quit with NRT OTC 3297 smokers in US 2-mg, 4-mg nicotine gum or placebo The first 8 weeks gardually reduce number of CPD and increase number of pieces of gum Abstinent 24 hours use gum as FDA recom Shiffman et al. Am J Prev Med 2009

19. P Tonnesen.2009 Reduction to quit with NRT OTC Results: Odds ratio for quitting vs. placebo 1 Month 6 Months 2-mg gum2.01 1.80 4-mg gum4.665.90 Reducers more likely to quit Shiffman et al. 2009

20. P Tonnesen.2009 A review of 11 studies of NRT used for smoking reduction found no unexpected adverse events, while side effects that may possibly be related to nicotine overdose (such as nausea and vomiting) were evenly distributed between active and placebo treatment groups (Fagerström & Hughes 2002) No increase in cardiovascular events (Murray et al 1996) in concurrent use of NRT and smoking for up to five years Adverse events

21. P Tonnesen.2009 Use of nicotine 4 mg gum and smoking every hour (in order to attain unusually high plasma nicotine levels) revealed no evidence of adverse cardiac effects, even during exercise tests (Stahl et al 2001). The total nicotine intake remains broadly stable when smokers use NRT to reduce their cigarette smoking (Benowitz et al 1998) Adverse events cont

22. P Tonnesen.2009 Conclusion : Smoking reduction Reduction possible long-term Reduction leads to cessation NRT increase success rates Motivation to quit not decreased, but actually increased (55-80%) Recruitment of new segment of smokers Effect on health ? (if < 6 cig/day ?)

23. P Tonnesen.2009 NRT and smoking reduction 1.Fast acting NRT: gum or inhaler, sublingual, loozenge (nasal spray) (mouth spray) 2. Use for 2-3 months: If reduced to less than 50 % then continue with NRT

24. P Tonnesen.2009 Treatment of most smokers is possible Motivated to quit Motivated to reduce Smoking Reduction Smoking cessation Agressive smoking cessation with NRT: Combinations of 2 NRTs; bupropionSR; varenicline; Recycling NRT for 3-(18) months