Smoking cessation Smoking cessation and COPDand COPD

Philip Tønnesen, M.D., Philip Tønnesen, M.D., dr.med.dr.med.

Dept. Pulm. MedicineDept. Pulm. MedicineGentofte HospitalGentofte Hospital

Copenhagen, DenmarkCopenhagen, Denmark

I have received consulting and I have received consulting and speaking fees and research speaking fees and research

grants from many companies grants from many companies who develop smoking cessation who develop smoking cessation

medications, products and medications, products and services services

DisclosureDisclosure

DisclosureDisclosure

First line drugs: Efficacy figures First line drugs: Efficacy figures from the Cochrane registerfrom the Cochrane register

Sustained quit rates for 1-year (Risk Ratio)Sustained quit rates for 1-year (Risk Ratio)

NRT versus placeboNRT versus placebo11 1.581.58

(111 studies)(111 studies) (95 % CI, 1.50-1.66)(95 % CI, 1.50-1.66)

Any type of NRTAny type of NRT

Bupropion SR versus placeboBupropion SR versus placebo22 1.851.85

(31 studies)(31 studies)

VareniclineVarenicline versus placeboversus placebo33 2.332.33

(9 studies)(9 studies) (95% CI, 1.95-2.80)(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) CD0000313. Cahill et al. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD006103.

First line drugs: Efficacy figures from US First line drugs: Efficacy figures from US clinical guidelines clinical guidelines

OR (95%CI)OR (95%CI)Abstinence Abstinence

raterate

PLACEBOPLACEBO aa

1.0 1.0 13.813.8

MONOTHERAPIESMONOTHERAPIES ““

VareniclineVarenicline 3.1 (2.5-3.8) 3.1 (2.5-3.8) 33.233.2

High dose nicotine patch High dose nicotine patch 2.3 (1.7-3.0)2.3 (1.7-3.0) 26.526.5

Nicotine gum (>14 weeks)Nicotine gum (>14 weeks) 2.2 (1.5-3.2)2.2 (1.5-3.2) 26.126.1

BupropionSRBupropionSR 2.0 (1.8-2.2)2.0 (1.8-2.2) 24.224.2

COMBINATION THERAPIES COMBINATION THERAPIES 22

Patch + ad lib NRTPatch + ad lib NRT 3.6 (2.5-5.2)3.6 (2.5-5.2) 36.536.5

Patch + BupropionSRPatch + BupropionSR 2.5 (1.9-3.4)2.5 (1.9-3.4) 28.928.9

Patch + inhalerPatch + inhaler 2.2 (1.3-3.6)2.2 (1.3-3.6) 25.8 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.

Smoking prevalence among COPD pt’s Smoking prevalence among COPD pt’s in large RCT trials with ICS/LABAin large RCT trials with ICS/LABA

Study N Age FEV1(%) SmokersStudy N Age FEV1(%) Smokers

INSPIRE 1,323 65 1.3 (39%) INSPIRE 1,323 65 1.3 (39%) 38%38%

ISOLDEISOLDE 751 64 1.4 (50%) 751 64 1.4 (50%) 38%38%

TORCH 5,343 65 1.2 (45%) TORCH 5,343 65 1.2 (45%) 45%45%

TRISTAN 1,465 63 1.4 (45%)TRISTAN 1,465 63 1.4 (45%) 51%51%

EUROSCOP 647 53 2.5 (80%) EUROSCOP 647 53 2.5 (80%) 54%54%

VESTBO 290 59 2.4 (86%)VESTBO 290 59 2.4 (86%) 77%77%

Network meta-analysis of RCT’s in COPD (1)Network meta-analysis of RCT’s in COPD (1)

8 trials included COPD8 trials included COPD

N=7,372N=7,372 Prolonged abstinence rate Prolonged abstinence rate

Lung Health Study (N=5,887) 12 M: 34 % versus 9 % (NRT)Lung Health Study (N=5,887) 12 M: 34 % versus 9 % (NRT) Hilberink (N=392) 6 M: 16 % versus 9 % (NRT)Hilberink (N=392) 6 M: 16 % versus 9 % (NRT) Tønnesen (N=370)Tønnesen (N=370) 12 M: 14 % versus 5 % (NRT) 12 M: 14 % versus 5 % (NRT) Taskin Taskin (N=404) 6 M: 16 % versus 9 % (BUP) (N=404) 6 M: 16 % versus 9 % (BUP) Wagena (N=255) 6 M: 30 % versus 19 %(BUP)Wagena (N=255) 6 M: 30 % versus 19 %(BUP) Pederson (N=64) Pederson (N=64) 6 M: 27 % versus 16 % 6 M: 27 % versus 16 % Crowley (N=49)Crowley (N=49) 6 M: 14 % versus 14 % 6 M: 14 % versus 14 % Brandt (N=56)Brandt (N=56) 12 M: 32 % versus 16 % 12 M: 32 % versus 16 % (Taskin (N=499) 12 M: 19 % versus 6 % (VAR))***(Taskin (N=499) 12 M: 19 % versus 6 % (VAR))***

Eur Respir J 2009;34:634-40Eur Respir J 2009;34:634-40

Efficacy of smoking cessation in COPD (2)Efficacy of smoking cessation in COPD (2)

Odds ratioOdds ratio Nothing/ usual careNothing/ usual care

Counselling aloneCounselling alone 1.82 (0.96-3.34), P=0.071.82 (0.96-3.34), P=0.07

Counselling +antidepres.Counselling +antidepres. 3.32 (1.53-7.21), P=0.0023.32 (1.53-7.21), P=0.002

Counselling + NRTCounselling + NRT 5.08 (4.32-5.97), P<0.0015.08 (4.32-5.97), P<0.001

Counselling + varenicline Counselling + varenicline

(1 study only) (CHEST, 2011)(1 study only) (CHEST, 2011)

4.04 (2.13-7.67) P<0.0014.04 (2.13-7.67) P<0.001

Eur Respir J 2009;34:634-40

COPD cont.COPD cont.

Smoking cessation in COPDSmoking cessation in COPD

Tønnesen et al, Chest 2006:Tønnesen et al, Chest 2006:

Nurse-conducted smoking cessation in patients with Nurse-conducted smoking cessation in patients with COPD, using nicotine sublingual tablets and behavioral COPD, using nicotine sublingual tablets and behavioral supportsupport

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

370 COPD patients370 COPD patients

Age :62 yearsAge :62 years

FEVFEV11: 1.57 (56 % predicted): 1.57 (56 % predicted)

Cigarettes/day: 20Cigarettes/day: 20

FTND: 6.4FTND: 6.4

High – low support, NRT – placebo 12 weeksHigh – low support, NRT – placebo 12 weeks

Smoking cessation in COPDSmoking cessation in COPD

NRT versus placebo:NRT versus placebo:

6 months quit rate: 6 months quit rate: 23 % vs 10 %23 % vs 10 %

12 months quit rate:12 months quit rate: 17 % vs 10 % (OR 2.0)17 % vs 10 % (OR 2.0)

2 week to 12 months: 14 % vs. 5 %2 week to 12 months: 14 % vs. 5 %

SGRQ in COPD (12 Months)SGRQ in COPD (12 Months)

QuittersQuitters Reducers Reducers SmokersSmokers

Symptoms -28Symptoms -28 -21 -21 -2 -2

ActivityActivity -6-6 -8 -8 -2 -2

ImpactImpact -8-8 -5 -5 -4 -4

Total score -10.9Total score -10.9 -8.5 -8.5 -2.9 -2.9

Varenicline and COPD (mild-moderate)Varenicline and COPD (mild-moderate)Chest 2010, Tashkin et alChest 2010, Tashkin et al

12 weeks 12 weeks VareniclineVareniclinePlaceboPlacebo

NumbersNumbers 250250 254254

AgeAge 5757 5757

FEV1 % FEV1 % 71 %71 % 69 %69 %

Cig/dayCig/day 2525 2424

QuittersQuitters

3-12 Months3-12 Months 18.6 %18.6 % 5.6 %5.6 %

Effect of smoking cessation interventionsEffect of smoking cessation interventions

GPs short advice: GPs short advice: 2 %2 %

Intensive behavioural support: Intensive behavioural support: 7 %7 %

Self-help materialSelf-help material 1 %1 %

Proactive telephone counselingProactive telephone counseling 2 %2 %

Nicotine productsNicotine products 7 %7 %

BupropionBupropion 9 %9 %

VareniclineVarenicline 11 %*11 %*

Intensive support+NRT/bupropion Intensive support+NRT/bupropion 13 -19 %13 -19 %

Intensive support + vareniclineIntensive support + varenicline 18 - 22 %*18 - 22 %*

Modified from West et al, Thorax 2000; *Cochrane Library 2007-2008

Lung Health study 1 (1)Lung Health study 1 (1)

10 clinical centers in US10 clinical centers in US

12 group sessions during the first 10 weeks12 group sessions during the first 10 weeks

4 sessions in the first week4 sessions in the first week

Target quit dayTarget quit day

CounsellingCounselling

Aggresive use of Nicotine 2-mg chewing gumAggresive use of Nicotine 2-mg chewing gum

Follow-up program with focus on relapse prevention, Follow-up program with focus on relapse prevention, stress mangement, weight gainstress mangement, weight gain

Formal re-treatment when relapsedFormal re-treatment when relapsed

Lung Health Study: Point prevalenceLung 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%

qu

itte

rs

1-year 2-year 3-year 4-year 5-year

S-IU-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)

Mean FEVMean FEV1 1 quitters and smokers (diff. 11-yrs: (3)quitters and smokers (diff. 11-yrs: (3)380 ml; diff smokers and interm: 100 ml;380 ml; diff smokers and interm: 100 ml;

0

0,5

1

1,5

2

2,5

3

3,5

Entry 1-year 2-year 3-year 4-year 5-year 11-years

FE

V-1 Quitters

Smokers

Smoking Cessation: Effects on Smoking Cessation: Effects on Mortality (4)Mortality (4)

CHD=coronary heart disease; CVD=cardiovascular disease.

4

2

1

0

Rat

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f D

eath

per

100

0 P

erso

n-Y

ears

OtherCHD CVD Lung Cancer

Other Cancer

Respiratory Disease

Unknown

Causes of Death

Sustained Quitter Intermittent Quitter Continuing Smokers

3

Athonisen et al. Ann Intern Med. 2005;142(4):233-239.

0

1

2

3

4

5

6

7

8

9

10

0 1 2 3 4 5Year

Me

an

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igh

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an

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Male smokersMale quittersFemale smokersFemale quitters

Weight change in the Lung Health Study (5)

Intensity of interventionIntensity of intervention

Minimal (<3 minutes) is effective (A)Minimal (<3 minutes) is effective (A)

Dose-response effect (person-to-person) (A)Dose-response effect (person-to-person) (A)

Four or more sessions are especially effective (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.

Brief intervention = 2 questionsBrief intervention = 2 questions

””Do you smoke?” and if yesDo you smoke?” and if yes

” ” Have you considered to quit?”Have you considered to quit?”

Very simple and short:Very simple and short:

It’s the patients project to quit but your obligation to It’s the patients project to quit but your obligation to support the smoker in the quitting attemptsupport the smoker in the quitting attempt

Arrange referal to smoking cessation: a new Arrange referal to smoking cessation: a new appointment, smoking cessation clinic, etc. appointment, smoking cessation clinic, etc.

Good idea to have a card with address and phone Good idea to have a card with address and phone numbernumber

Smoking cessation by hospitalization (1) Smoking cessation by hospitalization (1) COPD patients: COPD patients: Hospitalization (N=247) vs. Usual careHospitalization (N=247) vs. Usual care (N=231) (N=231)

FEV1 % pred.:75 % Age: 52 yearsFEV1 % pred.:75 % Age: 52 years

Hospitalization in Åre Hospital in Northern SwedenHospitalization in Åre Hospital in Northern Sweden

11 days, third day: target quit day, NRT; exercise, 1 hour daily meeting 11 days, third day: target quit day, NRT; exercise, 1 hour daily meeting with trained cessation nurses, educational program followed by weekly with trained cessation nurses, educational program followed by weekly telephone calls by nursestelephone 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;10:883-890Sundblad, Larsson K, Nathell L, Nic Tob Res 2008;10:883-890

Smoking cessation by hospitalization (2)Smoking cessation by hospitalization (2)

Smoking cessation groupSmoking cessation group

1-year quit rate: 52 %1-year quit rate: 52 %

3-year quit rate: 38 %3-year quit rate: 38 %

Used NRT: 28 %Used NRT: 28 %

Used BUP: 5 %Used BUP: 5 %

Sundblad, Larsson K, Nathell L, Nic Tob Res Sundblad, Larsson K, Nathell L, Nic Tob Res 2008;10:883-8902008;10:883-890

Usual careUsual care

1-year quit rate: 7 %1-year quit rate: 7 %

3-year quit rate: 10 %3-year quit rate: 10 %

Used NRT: 14 %Used NRT: 14 %

Used BUP: 5 %Used BUP: 5 %

What are we doing today in smoking What are we doing today in smoking cessation?cessation?

Cost-effectivenessCost-effectiveness

Meta-analysis of cost effectivness of smoking Meta-analysis of cost effectivness of smoking cessation after 25 yearscessation after 25 years

Quit rate Cost per QUALYQuit rate Cost per QUALYUsual careUsual care 1.4 % 1.4 %Minimal counsellingMinimal counselling 2.6 % 2.6 % 16.900 Euros 16.900 EurosIntensive counsellingIntensive counselling 6.0 % 6.0 % 8.200 Euros 8.200 EurosIntesive c. + pharma. 12.3 % 2.400 EurosIntesive c. + pharma. 12.3 % 2.400 Euros

Hoogendoorn M et al. Thorax 2010;65:711-718

The US experimentThe US experiment

Re-imbursement Re-imbursement

InInssurance coverage of smoking cessationurance coverage of smoking cessation r resulted inesulted in::1.1. Higher rates of use of evidence-based therapies Higher rates of use of evidence-based therapies 2.2. Higher Higher overall overall quit ratesquit rates3.3. Smoking Smoking cessation coverage in US 25 % (1997) to 90 % cessation coverage in US 25 % (1997) to 90 %

(2003)(2003)22

1. Kaper et al 2006 1. Kaper et al 2006 Pharmacoeconomics 24(5): 453-64Pharmacoeconomics 24(5): 453-64

2. McPhillips-Tangum et al. Prev Chronic Dis 2006 3; 1-11. Available from: 2. McPhillips-Tangum et al. Prev Chronic Dis 2006 3; 1-11. Available from: http://www.cdc.gov/pcd/issues/2006/jul/05_0173.htmhttp://www.cdc.gov/pcd/issues/2006/jul/05_0173.htm

ERS Guidelines ERS Guidelines

Aggressive smoking cessation is recommended i.e. Aggressive smoking cessation is recommended i.e. varenicline, NRT, bupropionSR, and counseling and varenicline, NRT, bupropionSR, and counseling and recycling recycling

Data from NIV-COPD national register in Data from NIV-COPD national register in Denmark for 2010Denmark for 2010

Ambulatory COPD patients in DKAmbulatory COPD patients in DK

Asked about smoking habitAsked about smoking habit Oct.-Dec. July-Sept.Oct.-Dec. July-Sept. Jan.-JuneJan.-June

(N=6167) 75 % (N=6167) 75 % 75 % 75 % 66 % 66 %

Adviced to quit smokingAdviced to quit smoking

(1467)(1467) 91 % 91 % 92 % 92 % 88 % 88 %

Conclusion smoking cessation in COPDConclusion smoking cessation in COPD

Counselling + NRT increases quit rateCounselling + NRT increases quit rate

Counselling + BupropionSR increases quit rateCounselling + BupropionSR increases quit rate

Counselling + Varenicline increases quit rateCounselling + Varenicline increases quit rate

(study under publication)(study under publication)

Retreatment after relapse increases long-term quit rateRetreatment after relapse increases long-term quit rate

Expect a 1-year quit rate of 15-35 % (point prevalence)Expect a 1-year quit rate of 15-35 % (point prevalence)

Tønnesen et al. ERS guidelines. ERJ 2008Tønnesen et al. ERS guidelines. ERJ 2008

Take home meassage: Smoking Take home meassage: Smoking cessation in COPDcessation in COPD

Counselling + NRT/ BupropionSR or Varenicline for 6 Counselling + NRT/ BupropionSR or Varenicline for 6 months should be perscribed to COPD smokers months should be perscribed to COPD smokers

Retreatment if the COPD patient relapseRetreatment if the COPD patient relapse

Tønnesen et al. ERS guidelines. ERJ 2008Tønnesen et al. ERS guidelines. ERJ 2008

“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