1. Smoking cessation and COPD Philip Tønnesen, M.D., dr.med. Dept. Pulm. Medicine Gentofte Hospital Copenhagen, Denmark

2. I have received consulting and speaking fees and research grants from many companies who develop smoking cessation medications, products and services Disclosure

3. Disclosure

4. First line drugs: Efficacy figures from the Cochrane register Sustained quit rates for 1-year (Risk Ratio) NRT versus placebo 1 1.58 (111 studies)(95 % CI, 1.50-1.66) Any type of NRT Bupropion SR versus placebo 2 1.85 (31 studies) Varenicline versus placebo 3 2.33 (9 studies)(95% CI, 1.95-2.80) 1.Silagy et al. Cochrane Database Syst Rev. 2008;jan 23(0):CD000146. 2.Hughes et al. Cochrane Database Syst Rev. 2008;(3) CD000031 3.Cahill et al. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD006103.

5. First line drugs: Efficacy figures from US clinical guidelines OR (95%CI)Abstinence rate PLACEBO a 1.0 13.8 MONOTHERAPIES “ Varenicline3.1 (2.5-3.8) 33.2 High dose nicotine patch 2.3 (1.7-3.0)26.5 Nicotine gum (>14 weeks)2.2 (1.5-3.2)26.1 BupropionSR2.0 (1.8-2.2)24.2 COMBINATION THERAPIES 2 Patch + ad lib NRT3.6 (2.5-5.2)36.5 Patch + BupropionSR2.5 (1.9-3.4)28.9 Patch + inhaler2.2 (1.3-3.6)25.8 Fiore MC, Bailey WC, Cohen SJ, et al. Clinical Practice Guideline.Treating Tobacco use and Dependence.: 2008 Update. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May 2008.

6. Smoking prevalence among COPD pt’s in large RCT trials with ICS/LABA Study N Age FEV1(%) Smokers Study N Age FEV1(%) Smokers  INSPIRE 1,323 65 1.3 (39%) 38%  ISOLDE 751 64 1.4 (50%)38%  TORCH 5,343 65 1.2 (45%) 45%  TRISTAN 1,465 63 1.4 (45%)51%  EUROSCOP 647 53 2.5 (80%) 54%  VESTBO 290 59 2.4 (86%)77%

7. Network meta-analysis of RCT’s in COPD (1) 8 trials included COPD 8 trials included COPD N=7,372 Prolonged abstinence rate N=7,372 Prolonged abstinence rate  Lung Health Study (N=5,887) 12 M: 34 % versus 9 % (NRT)  Hilberink (N=392) 6 M: 16 % versus 9 % (NRT)  Tønnesen (N=370) 12 M: 14 % versus 5 % (NRT)  Taskin (N=404) 6 M: 16 % versus 9 % (BUP)  Wagena (N=255) 6 M: 30 % versus 19 %(BUP)  Pederson (N=64) 6 M: 27 % versus 16 %  Crowley (N=49) 6 M: 14 % versus 14 %  Brandt (N=56) 12 M: 32 % versus 16 %  (Taskin (N=499) 12 M: 19 % versus 6 % (VAR))***  Eur Respir J 2009;34:634-40

8. Efficacy of smoking cessation in COPD (2) Odds ratio Nothing/ usual care Counselling alone 1.82 (0.96-3.34), P=0.07 Counselling +antidepres. 3.32 (1.53-7.21), P=0.002 Counselling + NRT 5.08 (4.32-5.97), P<0.001 Counselling + varenicline (1 study only) (CHEST, 2011) 4.04 (2.13-7.67) P<0.001 Eur Respir J 2009;34:634-40

9. COPD cont. COPD cont.

10. Smoking cessation in COPD Tønnesen et al, Chest 2006: Nurse-conducted smoking cessation in patients with COPD, using nicotine sublingual tablets and behavioral support

11. Smoking cessation/reduction in COPD (Tønnesen et al. Chest, 2006)  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

12. Smoking cessation in COPD NRT versus placebo: 6 months quit rate: 23 % vs 10 % 12 months quit rate:17 % vs 10 % (OR 2.0) 2 week to 12 months: 14 % vs. 5 %

13. SGRQ in COPD (12 Months) Quitters ReducersSmokers Symptoms -28 -21 -2 Activity-6 -8 -2 Impact-8 -5 -4 Total score -10.9 -8.5 -2.9

14. Varenicline and COPD (mild-moderate) Chest 2010, Tashkin et al 12 weeks VareniclinePlacebo  Numbers250254  Age5757  FEV1 % 71 %69 %  Cig/day2524  Quitters 3-12 Months18.6 %5.6 %

15. Effect of smoking cessation interventions  GPs short advice: 2 %  Intensive behavioural support: 7 %  Self-help material1 %  Proactive telephone counseling2 %  Nicotine products7 %  Bupropion9 %  Varenicline11 %*  Intensive support+NRT/bupropion 13 -19 %  Intensive support + varenicline18 - 22 %* Modified from West et al, Thorax 2000; *Cochrane Library 2007-2008

16. Lung Health study 1 (1)  10 clinical centers in US  12 group sessions during the first 10 weeks  4 sessions in the first week  Target quit day  Counselling  Aggresive use of Nicotine 2-mg chewing gum  Follow-up program with focus on relapse prevention, stress mangement, weight gain  Formal re-treatment when relapsed

17. Lung Health Study: Point prevalence Recycling of smokers every 4 months in 5 years! NRT:2mg-GUM (N=5587) 0 5 10 15 20 25 30 35 40 % quitters 1-year2-year3-year4-year5-year S-I U-C Anthonisen NR, Connett JE, Kiley JP,et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA 1994; 272: 1497 ‑ 1505. 8 weekly individual visits with 2 mg nico-gum (2)

18. Mean FEV 1 quitters and smokers (diff. 11-yrs: (3) 380 ml; diff smokers and interm: 100 ml;

19. Smoking Cessation: Effects on Mortality (4) CHD=coronary heart disease; CVD=cardiovascular disease. 4 2 1 0 Rate of Death per 1000 Person-Years OtherCHDCVD Lung Cancer Other Cancer Respiratory Disease Unknown Causes of Death Sustained QuitterIntermittent QuitterContinuing Smokers 3 Athonisen et al. Ann Intern Med. 2005;142(4):233-239.

20. Weight change in the Lung Health Study (5)

21. Intensity of intervention Minimal (<3 minutes) is effective (A) Dose-response effect (person-to-person) (A) Four or more sessions are especially effective (A)   Fiore MC, Bailey WC, Cohen SJ, et al. Clinical Practice Guideline.Treating Tobacco use and Dependence.: 2008 Update. Rockville, MD: U.S. Department of Healthand Human Services. Public Health Service. May 2008.

22. Brief intervention = 2 questions  ”Do you smoke?” and if yes  ” Have you considered to quit?”  Very simple and short:  It’s the patients project to quit but your obligation to support the smoker in the quitting attempt  Arrange referal to smoking cessation: a new appointment, smoking cessation clinic, etc.  Good idea to have a card with address and phone number

23. Smoking cessation by hospitalization (1)  COPD patients: Hospitalization (N=247) vs. Usual care (N=231) FEV1 % pred.:75 % Age: 52 years  Hospitalization in Åre Hospital in Northern Sweden  11 days, third day: target quit day, NRT; exercise, 1 hour daily meeting with trained cessation nurses, educational program followed by weekly telephone calls by nurses After 2-3 months 2-4 days in hospital After 2-3 months 2-4 days in hospital  Sundblad, Larsson K, Nathell L, Nic Tob Res 2008;10:883-890

24. Smoking cessation by hospitalization (2) Smoking cessation group 1-year quit rate: 52 % 3-year quit rate: 38 % Used NRT: 28 % Used BUP: 5 % Sundblad, Larsson K, Nathell L, Nic Tob Res 2008;10:883-890 Usual care 1-year quit rate: 7 % 3-year quit rate: 10 % Used NRT: 14 % Used BUP: 5 %

25. What are we doing today in smoking cessation?

26. Cost-effectiveness Cost-effectiveness

27. Meta-analysis of cost effectivness of smoking cessation after 25 years Quit rate Cost per QUALY Usual care 1.4 % Minimal counselling 2.6 % 16.900 Euros Intensive counselling 6.0 % 8.200 Euros Intesive c. + pharma. 12.3 % 2.400 Euros Meta-analysis of cost effectivness of smoking cessation after 25 years Quit rate Cost per QUALY Usual care 1.4 % Minimal counselling 2.6 % 16.900 Euros Intensive counselling 6.0 % 8.200 Euros Intesive c. + pharma. 12.3 % 2.400 Euros Hoogendoorn M et al. Thorax 2010;65:711-718

28. The US experiment  Re-imbursement  Insurance coverage of smoking cessation resulted in: 1.Higher rates of use of evidence-based therapies 2.Higher overall quit rates 3.Smoking cessation coverage in US 25 % (1997) to 90 % (2003) 2 1. Kaper et al 2006 Pharmacoeconomics 24(5): 453-64 2. McPhillips-Tangum et al. Prev Chronic Dis 2006 3; 1-11. Available from: http://www.cdc.gov/pcd/issues/2006/jul/05_0173.htm

29. ERS Guidelines  Aggressive smoking cessation is recommended i.e. varenicline, NRT, bupropionSR, and counseling and recycling

30. Data from NIV-COPD national register in Denmark for 2010  Ambulatory COPD patients in DK  Asked about smoking habit Oct.-Dec. July-Sept.Jan.-June Oct.-Dec. July-Sept.Jan.-June  (N=6167) 75 % 75 % 66 %  Adviced to quit smoking  (1467) 91 % 92 % 88 %

31. Conclusion smoking cessation in COPD  Counselling + NRT increases quit rate  Counselling + BupropionSR increases quit rate  Counselling + Varenicline increases quit rate (study under publication) (study under publication)  Retreatment after relapse increases long-term quit rate  Expect a 1-year quit rate of 15-35 % (point prevalence)  Tønnesen et al. ERS guidelines. ERJ 2008

32. Take home meassage: Smoking cessation in COPD  Counselling + NRT/ BupropionSR or Varenicline for 6 months should be perscribed to COPD smokers  Retreatment if the COPD patient relapse  Tønnesen et al. ERS guidelines. ERJ 2008

33. “Last Request: Please Don’t Smoke” My step-father asked me to take this picture of him after he regained consciousness in ICU. He lost the fight with lung disease (Asbestosis, COPD, and Pnuemonia) Friday morning. I will be away for a little while