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

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.

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

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

Effects of stopping smoking on survival of British doctors 50 year follow-up at age 25-34 (effect from age 35), at age 35-44 (effect from age 40), at age 45-54 (effect from age 50), at age 55-64 (effect from age 60) Doll, R. et al. BMJ 2004;328:1519

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

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

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 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

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

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

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

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

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

WHY DO SMOKERS KEEP SMOKING? Pharmacologic nicotine dependence DOPAMINE

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

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

Pharmacologic nicotine dependence WHY DO SMOKERS KEEP SMOKING? Pharmacologic nicotine dependence 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

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 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

1st Line - 2008 US Public Health Service Guidelines PHARMACOTHERAPY 1st 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

PLASMA NICOTINE LEVELS Cigarettes vs. Nicotine Replacement Products

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

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 Quit rates higher if add counseling Reduces post-cessation weight gain 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 Antagonist Prevents nicotine from binding to the receptor → Blocks reward, reinforcement of smoking

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

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=1.77 (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

Continuous abstinence VARENICLINE vs. NICOTINE PATCH Open label randomized controlled trial (5 countries, n= 746) 56 43 26 20 End of treatment OR 1.70 (1.26-2.28) Continuous abstinence OR 1.40 (0.99-1.99) Aubin HJ. Thorax 2008

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

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

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?

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

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 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

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

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”

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

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

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.)

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

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

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

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

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

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

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

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

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?

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

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