TREATMENT OF TOBACCO USE: EVIDENCE AND POLICY Nancy Rigotti, MD Director, Tobacco Research &...

TREATMENT OF TOBACCO USE:

EVIDENCE AND POLICY

Nancy Rigotti, MD

Director, Tobacco Research & Treatment Center

Massachusetts General Hospital

Professor of Medicine, Harvard Medical School

Boston, MA, USA

OVERVIEW

Tobacco use in perspective

What treatments are effective?

Role of tobacco treatment in global tobacco control (Why treatment matters)

What is the current status of treatment delivery worldwide?

TOBACCO USE IN PERSPECTIVE

#1 preventable cause of death in the world



5.4 million deaths per year worldwide (1 in 10 deaths)

If present trends continue…

> 8 million deaths per year by 2030

> 80% of deaths will be in developing countries

1 billion deaths in the 21st century (vs 100 million in the 20th century)

WHO, MPOWER Report, 2008

CAUSES OF DEATH ATTRIBUTABLE TO SMOKING – U.S.A.

Other cancer8%

Other diagnoses19%

Chronic lung disease

21%Stroke

4%

Coronary heart disease

20%

Lung cancer28%

HEALTH CONSEQUENCES OF TOBACCO Special issues for developing countries

Tuberculosis

Exposure → Infection → Disease → Death

risk of infection, if exposed (RR=1.7)1

risk of developing disease, if infected (RR=1.5)1

risk of dying of tuberculosis (RR 3.0 female, 2.3 male)2

India: TB is the leading cause of tobacco-related death 2

Cost of tobacco contributes to poverty, hunger, illness

1 Bates MN et al. Arch Intern Med 2007:167:335. 2 Jha P et al. NEJM 2008;358:1137



Cessation reduces health risks

Doll, R. et al. BMJ 2004;328:1519

Effects of stopping smoking on survival

of British doctors50 year follow-up

at age 25-34 (effect from age 35),



at age 55-64 (effect from age 60)

IS IT EVER TOO LATE TO BENEFIT FROM QUITTING?

Over age 65?

After chronic disease develops?

After MI, quitters lower CV mortality by 36%

With COPD, quitters slow decline in FEV1

Smokers have a poorer response to chemotherapy


Many people use tobacco


Cessation reduces health risks – even after chronic disease develops

PREVALENCE OF TOBACCO USE

1.3 billion people use tobacco

Tobacco use is growing worldwide

PREVALENCE OF TOBACCO USE

1.3 billion people use tobacco

Tobacco use is growing worldwide

Decreasing in much of the Decreasing in much of the developeddeveloped world world

35% of males, 22% of females use tobacco35% of males, 22% of females use tobacco

Increasing in much of the Increasing in much of the developingdeveloping world world

50% of males, 9% of females use tobacco50% of males, 9% of females use tobacco

TOBACCO USE IS MORE THAN CIGARETTE SMOKING

• Waterpipe

• Hookah• Narghile• Shisha pipe

Perceived to be safer thansmoking cigarettes

More acceptable for women

• Clove cigarettes• Bidi• Kretek

• Smokeless tobacco


Many people use tobacco


Cessation reduces health risks

A global epidemic that requires action

The shift of the tobacco epidemic to the The shift of the tobacco epidemic to the developing world will lead to unprecedented developing world will lead to unprecedented disease and early death in countries wheredisease and early death in countries where

• Population growth is highestPopulation growth is highest

• Potential for increased tobacco use is highestPotential for increased tobacco use is highest

• Health-care services are least availableHealth-care services are least available

Secretariat’s Report on FCTC Article 14, Secretariat’s Report on FCTC Article 14, 20082008

OVERVIEW




QUITTING IN PERSPECTIVEU.S. data

40% of smokers try to quit each year

70% of current smokers want to quit

Few succeed long-term (quit for 1 year)

5% quit without help

30% quit with best treatment

Only 25% of those trying to quit seek help

WHY DO SMOKERS KEEP SMOKING?

Pharmacologic nicotine dependence

DOPAMINE


Irritability, anger, impatience Restlessness Difficulty concentrating Insomnia Anxiety Depressed mood Increased appetite

Pharmacologic nicotine dependence → Craving (nicotine “hunger”)

→ Nicotine withdrawal symptoms



Psychological factors

• Cues (meals, alcohol, other smokers)

• Coping with stress, emotions (anger)



Psychological factors

Psychiatric co-morbidity

• Depression

• Schizophrenia

• Substance abuse

THE CHALLENGE FOR TREATMENT

We have effective treatments, but…

We need better treatments

We need to deliver the treatments we have to more of the smokers who need them

CAVEAT

The evidence about treatment comes largely from studies in high-income countries

Few trials have been done in middle- or low-income countries

Less awareness of health risks Fewer have tried to quit and failed

Biology is relatively constant

Cultural context varies across countries

SMOKING CESSATION METHODS2008 US Public Health Service Guidelines

Effective treatments

More is better but brief intervention works

Treating tobacco is highly cost-effective

Counseling (individual / group / telephone)

Pharmacotherapy

Combination - better than either one alone

PHARMACOTHERAPY1st Line - 2008 US Public Health Service Guidelines

Nicotine replacement OR Skin patch 1.9

Gum 1.5

Oral inhaler 2.1

Nasal spray 2.3

Lozenge 2.0

Bupropion SR (Zyban,Wellbutrin SR) 2.0

Varenicline (Chantix/Champix) 3.1

0

2

4

6

8

10

12

14

16

18

0 10 20 30 40 50 60 70 80 90 100 110 120

Time post administration (min)

Pla

sma

nico

tine

leve

l (ng

/mL) Cigarette (1-2 mg)

Nasal spray (1 mg)

Gum (4 mg)

Patch (21 mg)

PLASMA NICOTINE LEVELSCigarettes vs. Nicotine Replacement Products

NICOTINE REPLACEMENT

Long-acting, slow onset → skin patch

Short-acting Intermediate onset → oral (gum, lozenge, inhaler)

More rapid onset → nasal (spray)

Constant nicotine level to avoid withdrawal Simplest to use, best compliance User has no control of dose

User controls dose Nicotine blood levels fluctuate more Requires more training to use properly

New Ways to Use Older Drugs

NICOTINE REPLACEMENT(Supported by evidence and USPHS*)

*Combine short- and long-acting forms“Patch plus” regimen

*Use higher patch doses

*Extend treatment to prevent relapse

Start patch 2 weeks before quit day

“Reduce to quit” (gradual reduction)

BUPROPION SR (Zyban, Wellbutrin SR)

Doubles cessation rate independent of its antidepressant effect

Reduces post-cessation weight gain

Quit rates higher if add counseling

Reduces seizure threshold (risk: 1/1000)

VARENICLINE

Binds selectively to the α4β2 nicotinic receptor, which mediates nicotine dependence

Dual mechanism of action

Partial agonist Stimulates receptor to treat craving, withdrawal

AntagonistPrevents nicotine from binding to the receptor →Blocks reward, reinforcement of smoking

NH

N

N

4-Week Continuous Quit Rates Wks 9–12 (End of drug treatment)

CO-Confirmed

OR=3.85OR=3.85**

(95% CI 2.70, 5.50)

OR=1.93OR=1.93**

(95% CI 1.40, 2.68)

OR=3.85OR=3.85**

(95% CI 2.69, 5.50)

OR=1.90OR=1.90**

(95% CI 1.38, 2.62)

100

44 44

3030

1818

0

20

40

60

Study I Study II

Res

po

nse

Rat

e (%

)

Varenicline Bupropion Placebo

N=352 N=329 N=344 N=344 N=342 N=341

*p<0.0001

Continuous Abstinence Rates through 1 Year (Weeks 9-52)

CO-Confirmed

OR=3.09OR=3.09 (95% CI 1.95, 4.91) p<0.001

OR=1.46OR=1.46(95% CI 0.99, 2.17) p=0.057

OR=2.66OR=2.66 (95% CI 1.72, 4.11) p<0.001

OR=1.77OR=1.77 (95% CI 1.19,2.63) p=0.004

22 23

1516

108

0

20

40

Study I Study II

Res

po

nse

Rat

e (%

)

100

Varenicline Bupropion Placebo

N=352 N=329 N=344 N=344 N=342 N=341

VARENICLINE vs. NICOTINE PATCHOpen label randomized controlled trial

(5 countries, n= 746)

0

10

20

30

40

50

60

Weeks 9-12 Weeks 9-52

Varenicline NRT

Aubin HJ. Thorax 2008

End of treatmentOR 1.70 (1.26-2.28)

Continuous abstinenceOR 1.40 (0.99-1.99)

2620

56

43

VARENICLINE (Chantix, Champix)Entered U.S. market in 2006

What we don’t know Efficacy without regular behavioral support

Efficacy, tolerability in a broader spectrum of smokers than in the clinical trials - Being tested now in CVD, COPD patients

Very rare side effects?

- Depression, suidicality, abnormal behavior

Efficacy combined with NRT, bupropion

POTENTIAL FUTURE TREATMENTS

Nicotine vaccine

Cytisine Used in Eastern Europe; no good efficacy data yet

RCT in progress in Poland

A cheaper alternative to varenicline?

Rationale: keep nicotine out of the brain Indication: cessation or relapse prevention? Status: several vaccines in clinical trials

POPULATION IMPACT OF ANY TREATMENT

IMPACT = EFFICACY x REACH

Efficacy = % of those treated who benefit

Reach = % of population who get treatment

SITES FOR DELIVERING CESSATION EDUCATION AND TREATMENT

Health care system

Work site

Schools

Sports programs

Religious settings

Military

Other community-based settings

SITES FOR DELIVERING TOBACCO TREATMENT

Health care system

Primary care (adults, children)

Prenatal/obstetric care

Hospital, emergency room

Pre-operative care

TB, HIV treatment delivery programs

PHYSICIAN INTERVENTION

Routine advice to quit is effective Odds of quitting by 66% (vs no advice) *

Brief counseling is more effective Odds of quitting by 37% (vs brief advice) *

Brief intervention by other clinicians is effective

*

Cochrane reviews

TOBACCO USE TOBACCO USE BY HEALTH PROFESSIONALSBY HEALTH PROFESSIONALS

• A problem in many countriesA problem in many countries

• Health professionals act as role modelsHealth professionals act as role models

• Clinicians who smoke are less likely to Clinicians who smoke are less likely to counsel patientscounsel patients

• Treatment strategies must include Treatment strategies must include cessation programs for health care cessation programs for health care professionals and studentsprofessionals and students

5A BRIEF COUNSELING MODEL2000 U.S. Public Health Service Guidelines

ASK all patients about smoking

ADVISE all smokers to quit

ASSESS smoker’s readiness to

quit

ASSIST smokers to quit

ARRANGE follow-up care

PROBLEM

Few physicians follow the full guideline

Physicians say…

“I don’t have the time”

“I don’t know how”

“Treatment does not work or is not covered”


ASK

ADVISE Core physician role

ASSESS

ASSIST

ARRANGE


ASK Done by office staff (‘vital sign’)


ASSESS

ASSIST

ARRANGE


ASK Done by office staff


ASSESS

ASSIST Refer to community

resources

ARRANGE (clinics, quit lines, etc.)

TELEPHONE QUITLINESDelivering counseling proactively by phone

Convenient

Private Free (paid for by government or health plans)

Effective (pooled OR 1.4, 95% CI 1.3-1.6)*

Offered by states, now a national access number (1-800-QUIT-NOW)

*Stead LF et al. Tobacco Control 2007;16(suppl 1):i3

QUITWORKS

Referral formfaxed to Quitline

Quitline calls smoker to offer free counseling

QuitWorks gives MD feedback on patient progress

ABC’sNew Zealand Clinical Guidelines, 2007

ASK all patients about smoking

BRIEF ADVICE to quit

CESSATION SUPPORT

• Prescribe medication

• Connect to counseling support

OVERVIEW




World Health Organization World Health Organization Framework Convention on Framework Convention on Tobacco Control (FCTC)Tobacco Control (FCTC)

Article 14 obliges countries toArticle 14 obliges countries to

• develop evidence-based treatment develop evidence-based treatment guidelines guidelines

• take effective measures to promote take effective measures to promote adequate treatment for tobacco adequate treatment for tobacco dependencedependence


Article 14 Article 14 asks countries to try toasks countries to try to• Implement programs to promote cessation in Implement programs to promote cessation in

multiple settings multiple settings (schools, workplaces, health care, sports)(schools, workplaces, health care, sports)

• Implement diagnosis and treatment of tobacco Implement diagnosis and treatment of tobacco dependence in national health, education programsdependence in national health, education programs

• Establish treatment and prevention programs in Establish treatment and prevention programs in health care and rehabilitation facilitieshealth care and rehabilitation facilities

• Facilitate access and availability to treatmentFacilitate access and availability to treatment


There is an interaction between Article 14 There is an interaction between Article 14 and other FCTC Articlesand other FCTC Articles

• Implementation of other articles will encourage Implementation of other articles will encourage quittingquitting

• Implementation of Article 14 will increase support Implementation of Article 14 will increase support for other Articlesfor other Articles

Implementation of other articles in the FCTC will encourage quitting

Article 6 Price and tax measures to reduce demand for tobacco

Article 8 Protection from exposure to tobacco smoke

Article 11 More prominent and pictorial warnings

Article 13 Reduce availability of tobacco advertising and marketing

Article 20 Research, surveillance and exchange of information

Implementation of FCTC Article 14 could increase support for the adoption of other articles

Article 6 Price and tax measures to reduce demand for tobacco

Article 8 Protection from exposure to tobacco smoke

Article 11 More prominent and pictorial warnings

Article 13 Reduce availability of tobacco advertising and marketing


• ImplementationImplementation of FCTC policies will be facilitated of FCTC policies will be facilitated by the availability of treatment servicesby the availability of treatment services

Tobacco taxesTobacco taxes

Smoke-free policiesSmoke-free policies

• Is it Is it ethical ethical to increase tobacco price and restrict to increase tobacco price and restrict use without providing access to treatment, especially use without providing access to treatment, especially price increases for the poor? price increases for the poor?

MPOWER ReportWorld Health Organization – 2008

M onitor tobacco use and tobacco control policy

P rotect people from tobacco smoke

O ffer help to quit tobacco use

W arn about the dangers of tobacco

E nforce bans on tobacco advertising, promotion

R aise taxes on tobacco

http://www.who.int/entity/tobacco/mpower/package/en/index.html

WHY TREATMENT MATTERS

Tobacco use is growing epidemic

Stopping tobacco use reduces health risks

Tobacco prevention by itself works slowly

CESSATON vs. PREVENTION

WHY TREATMENT MATTERS

Tobacco use is growing epidemic

Stopping tobacco use reduces health risks

Tobacco prevention by itself works slowly

Tobacco use is an addictive disorder

Tobacco treatment aids tobacco control policies overall (and vice versa)

CONCLUSIONS

Cessation is necessary to stop the global tobacco epidemic

Tobacco treatment is needed because of the addictive nature of tobacco use

Effective tobacco treatment exists

Reach and access to cost-effective treatment is the major challenges

Tobacco treatment is an necessary component of comprehensive tobacco control programs

TREATMENT OF TOBACCO USE: EVIDENCE AND POLICY Nancy Rigotti, MD Director, Tobacco Research &...

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