1. 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

2. 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?

3. TOBACCO USE IN PERSPECTIVE
#1 preventable cause of death in the world

4. 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

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

6. 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

7. TOBACCO USE IN PERSPECTIVE
#1 preventable cause of death in the world
Cessation reduces health risks

8. Effects of stopping smoking on survival of British doctors
50 year follow-up
at age (effect from age 35),
at age (effect from age 40),
at age (effect from age 50),
at age (effect from age 60)
Doll, R. et al. BMJ 2004;328:1519

9. TO BENEFIT FROM QUITTING?
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

10. TOBACCO USE IN PERSPECTIVE
#1 preventable cause of death in the world
Cessation reduces health risks – even after chronic disease develops
Many people use tobacco

11. PREVALENCE OF TOBACCO USE
1.3 billion people use tobacco
Tobacco use is growing worldwide

12. PREVALENCE OF TOBACCO USE
1.3 billion people use tobacco
Tobacco use is growing worldwide
Decreasing in much of the developed world
35% of males, 22% of females use tobacco
Increasing in much of the developing world
50% of males, 9% of females use tobacco

13. TOBACCO USE IS MORE THAN CIGARETTE SMOKING
Waterpipe
Hookah
Narghile
Shisha pipe
Perceived to be safer than
smoking cigarettes
More acceptable for women
Clove cigarettes
Bidi
Kretek
Smokeless tobacco

14. TOBACCO USE IN PERSPECTIVE
#1 preventable cause of death in the world
Cessation reduces health risks
Many people use tobacco
A global epidemic that requires action

15. Population growth is highest
The shift of the tobacco epidemic to the developing world will lead to unprecedented disease and early death in countries where
Population growth is highest
Potential for increased tobacco use is highest
Health-care services are least available
Secretariat’s Report on FCTC Article 14, 2008

16. OVERVIEW Tobacco use in perspective What treatments are effective?
Role of tobacco treatment in global tobacco control (Why treatment matters)

17. QUITTING IN PERSPECTIVE
U.S. data
70% of current smokers want to quit
40% of smokers try to quit each year
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

18. WHY DO SMOKERS KEEP SMOKING?
Pharmacologic nicotine dependence
DOPAMINE

19. WHY DO SMOKERS KEEP SMOKING?
Pharmacologic nicotine dependence → Craving (nicotine “hunger”)
→ Nicotine withdrawal symptoms
Irritability, anger, impatience
Restlessness
Difficulty concentrating
Insomnia
Anxiety
Depressed mood
Increased appetite

20. Pharmacologic nicotine dependence
WHY DO SMOKERS KEEP SMOKING?
Pharmacologic nicotine dependence
Psychological factors
Cues (meals, alcohol, other smokers)
Coping with stress, emotions (anger)

21. Pharmacologic nicotine dependence
WHY DO SMOKERS KEEP SMOKING?
Pharmacologic nicotine dependence
Psychological factors
Psychiatric co-morbidity
Depression
Schizophrenia
Substance abuse

22. 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

23. 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

24. 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

25. SMOKING CESSATION METHODS
2008 US Public Health Service Guidelines
Effective treatments
Counseling (individual / group / telephone)
Pharmacotherapy
Combination - better than either one alone
More is better but brief intervention works
Treating tobacco is highly cost-effective

26. 1st Line - 2008 US Public Health Service Guidelines
PHARMACOTHERAPY
1st Line US Public Health Service Guidelines
Nicotine replacement OR
Skin patch
Gum
Oral inhaler
Nasal spray
Lozenge
Bupropion SR (Zyban,Wellbutrin SR) 2.0
Varenicline (Chantix/Champix) 3.1

27. PLASMA NICOTINE LEVELS Cigarettes vs. Nicotine Replacement Products

28. NICOTINE REPLACEMENT Long-acting, slow onset → skin patch Short-acting
Constant nicotine level to avoid withdrawal
Simplest to use, best compliance
User has no control of dose
Short-acting
Intermediate onset → oral (gum, lozenge, inhaler)
More rapid onset → nasal (spray)
User controls dose
Nicotine blood levels fluctuate more
Requires more training to use properly

29. 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)

30. BUPROPION SR
(Zyban, Wellbutrin SR)
Doubles cessation rate independent of its antidepressant effect
Quit rates higher if add counseling
Reduces post-cessation weight gain
Reduces seizure threshold (risk: 1/1000)

31. VARENICLINE
Binds selectively to the α4β2 nicotinic receptor, which mediates nicotine dependence
Dual mechanism of action
Partial agonist
Stimulates receptor to treat craving, withdrawal
Antagonist
Prevents nicotine from binding to the receptor →
Blocks reward, reinforcement of smoking

32. 4-Week Continuous Quit Rates Wks 9–12 (End of drug treatment) CO-Confirmed
100
OR=3.85*
(95% CI 2.70, 5.50)
OR=3.85* (95% CI 2.69, 5.50) 60
OR=1.93* (95% CI 1.40, 2.68)
OR=1.90* (95% CI 1.38, 2.62) 40 44 44
Response Rate (%) 30 30 20 18 18
N=352
N=329
N=344
N=344
N=342
N=341
Study I
Study II
*p<0.0001
Varenicline
Bupropion
Placebo

33. Continuous Abstinence Rates through 1 Year (Weeks 9-52) CO-Confirmed
100
OR=3.09 (95% CI 1.95, 4.91) p<0.001
OR=2.66 (95% CI 1.72, 4.11) p<0.001 40
OR=1.46 (95% CI 0.99, 2.17) p=0.057
OR= (95% CI 1.19,2.63) p=0.004
Response Rate (%) 20 23 22 16 15 10 8
N=352
N=329
N=344
N=344
N=342
N=341
Study II
Study I
Varenicline
Bupropion
Placebo

34. Continuous abstinence
VARENICLINE vs. NICOTINE PATCH Open label randomized controlled trial (5 countries, n= 746) 56 43 26 20
End of treatment
OR ( )
Continuous abstinence
OR 1.40 ( )
Aubin HJ. Thorax 2008

35. 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

36. 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

37. POTENTIAL FUTURE TREATMENTS
Nicotine vaccine
Rationale: keep nicotine out of the brain
Indication: cessation or relapse prevention?
Status: several vaccines in clinical trials
Cytisine
Used in Eastern Europe; no good efficacy data yet
RCT in progress in Poland
A cheaper alternative to varenicline?

38. 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

39. POPULATION IMPACT OF ANY TREATMENT
IMPACT = EFFICACY x REACH
Efficacy = % of those treated who benefit
Reach = % of population who get treatment

40. SITES FOR DELIVERING CESSATION EDUCATION AND TREATMENT
Health care system
Work site
Schools
Sports programs
Religious settings
Military
Other community-based settings

41. 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

42. 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

43. TOBACCO USE BY HEALTH PROFESSIONALS
A problem in many countries
Health professionals act as role models
Clinicians who smoke are less likely to counsel patients
Treatment strategies must include cessation programs for health care professionals and students

44. 5A BRIEF COUNSELING MODEL
2000 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

45. 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”

46. 5A BRIEF COUNSELING MODEL
2000 U.S. Public Health Service Guidelines
ASK
ADVISE Core physician role
ASSESS
ASSIST
ARRANGE

47. 5A BRIEF COUNSELING MODEL
2000 U.S. Public Health Service Guidelines
ASK Done by office staff (‘vital sign’)
ADVISE Core physician role
ASSESS
ASSIST
ARRANGE

48. 5A BRIEF COUNSELING MODEL
2000 U.S. Public Health Service Guidelines
ASK Done by office staff
ADVISE Core physician role
ASSESS
ASSIST Refer to community resources
ARRANGE (clinics, quit lines, etc.)

49. Delivering counseling proactively by phone
TELEPHONE QUITLINES
Delivering counseling proactively by phone
Convenient
Private
Free (paid for by government or health plans)
Effective (pooled OR 1.4, 95% CI )*
Offered by states, now a national access number (1-800-QUIT-NOW)
*Stead LF et al. Tobacco Control 2007;16(suppl 1):i3

50. QUITWORKS Referral form faxed to Quitline Quitline calls
smoker to offer
free counseling
QuitWorks gives
MD feedback on
patient progress

51. New Zealand Clinical Guidelines, 2007
ABC’s
New Zealand Clinical Guidelines, 2007
ASK all patients about smoking
BRIEF ADVICE to quit
CESSATION SUPPORT
Prescribe medication
Connect to counseling support

52. OVERVIEW Tobacco use in perspective What treatments are effective?
Role of tobacco treatment in global tobacco control (Why treatment matters)

53. World Health Organization Framework Convention on Tobacco Control (FCTC)
Article 14 obliges countries to
develop evidence-based treatment guidelines
take effective measures to promote adequate treatment for tobacco dependence

54. World Health Organization Framework Convention on Tobacco Control (FCTC)
Article 14 asks countries to try to
Implement programs to promote cessation in multiple settings (schools, workplaces, health care, sports)
Implement diagnosis and treatment of tobacco dependence in national health, education programs
Establish treatment and prevention programs in health care and rehabilitation facilities
Facilitate access and availability to treatment

55. World Health Organization Framework Convention on Tobacco Control (FCTC)
There is an interaction between Article 14 and other FCTC Articles
Implementation of other articles will encourage quitting
Implementation of Article 14 will increase support for other Articles

56. Implementation of other articles in the FCTC will encourage quitting
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

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

58. World Health Organization Framework Convention on Tobacco Control (FCTC)
Implementation of FCTC policies will be facilitated by the availability of treatment services
Tobacco taxes
Smoke-free policies
Is it ethical to increase tobacco price and restrict use without providing access to treatment, especially price increases for the poor?

59. World Health Organization – 2008
MPOWER Report
World 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

60. WHY TREATMENT MATTERS Tobacco use is growing epidemic
Stopping tobacco use reduces health risks
Tobacco prevention by itself works slowly

61. CESSATON vs. PREVENTION

62. 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)

63. 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