Nancy Rigotti, MD

Professor of Medicine, Harvard Medical School Director, Tobacco Research and Treatment Center

Massachusetts General Hospital, Boston, MA nrigotti@partners.org

Primary Care Internal Medicine 2019

Treating Tobacco Use: Optimizing for the Best Outcomes

Disclosures - Nancy Rigotti, MD

Royalties - UpToDate, Inc.

Consultant - Achieve Life Sciences

Unpaid consultant, travel expenses - Pfizer, Inc.

Research grants – NIH

OVERVIEW

Challenges in treating tobacco users

Which treatments work? Clinical Practice Guidelines Optimizing Pharmacotherapy

Practical strategies for office practice

Electronic cigarettes – risks and benefits

WHY TREATING TOBACCO USE MATTERS

#1 preventable cause of death in the U.S. (and world)

34 million U.S. adults still smoke (14% of adults in 2017)

MMWR 2018;67(44):1225-32

WHY TREATING TOBACCO USE MATTERS

#1 preventable cause of death in the U.S. (and world)

34 million U.S. adults still smoke (14% of adults in 2017)

We’ve left vulnerable populations behind

MMWR 2018;67(44):1225-32

• Less educated, lower incomes • Other substance use disorders • Psychiatric illness • Homeless or incarcerated • LGBT

WHY TREATING TOBACCO USE MATTERS

#1 preventable cause of death in the U.S. (and world)

34 million U.S. adults still smoke (14% of adults in 2017)

Stopping smoking improves length and quality of life Even after chronic disease starts1 Even after age 652 Despite post-cessation weight gain3 It’s never too early or too late to quit

1 Critchley. JAMA 2003;290:86; 2 Gellert. Arch Intern Med 2012; 172:837; 3 Nu. NEJM 2018; 379:623.

WHY TREATING TOBACCO USE MATTERS

#1 preventable cause of death in the U.S. (and world)

34 million U.S. adults still smoke (14% of adults in 2017)

Stopping smoking improves length and quality of life

Delivering tobacco treatment in health care works

A CASE 55 yo man with HTN, BMI 30, depression (stable SSRI)

Smokes 15 cigarettes/day, started at age 18

“I know I should quit, but I’ve tried everything and nothing works.”

Used nicotine patch for 3 days → “I still wanted a cigarette”

Used bupropion for 1 month → “I didn’t want to smoke as much… I cut down but couldn’t quit”

Chantix? → “I heard that drug is dangerous!”

“What do you think about the electronic cigarette?”

QUESTIONS for you

• What’s an electronic cigarette? – Should you recommend it?

• Has he really tried everything?

• Is varenicline (Chantix) really risky?

• What’s your next step?

QUITTING IN PERSPECTIVE National Health Interview Survey - 2015

55% of smokers try to quit each year

Few succeed long-term (quit for 1 year)

~ 7% succeed without help

25-30% succeed long-term with best treatment

Only 31% of those trying to quit seek help

68% of current smokers want to quit

MMWR January 2017;65:1457

OVERVIEW

Challenges in treating tobacco users

Which treatments work? Clinical Practice Guidelines Optimizing Pharmacotherapy

Practical strategies for implementing in office practice

Electronic cigarettes

Smoking Cessation Treatment Guideline

2008 US Public Health Service, Endorsed by 2015 US Preventive Services Task Force

• Effective treatments exist

• More intensive treatment has better outcomes but even brief intervention works

• Pharmacotherapy – targets nicotine addiction • Behavioral support – targets behavioral components – delivery: in-person, by phone [SMS, web, apps]

• Combination is better than either one alone

Pharmacotherapy

1st Line Medications - 2008 US Public Health Service Guideline

• Nicotine replacement Skin patch (OTC)

Gum (OTC)

Lozenge (OTC) Oral inhaler (Rx)

Nasal spray (Rx)

• Bupropion SR (Zyban, Wellbutrin SR)

• Varenicline (Chantix)

All are FDA approved for cessation

All ~ double quit rate vs. placebo

Nicotine Replacement Products

Goal = ↓ nicotine withdrawal

All products ~ equally effective

Varenicline • Partial agonist at α4β2 nicotinic receptor

Receptor subtype that 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

NH

NN

Varenicline: Safety Concerns FDA Public Health Advisory - July 2009

• “[Varenicline] or [bupropion] has been associated with reports of changes in behavior such as hostility, agitation, depressed mood, and suicidal thoughts or actions.”

• “FDA is requiring the manufacturers of both products to add a new Boxed Warning”

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm169988.htm

EAGLES Trial (Anthenelli, Lancet 2016)

Continuous abstinence rate

• Double-blind placebo controlled RCT

• Nicotine patch vs bupropion vs varenicline vs placebo

• N=8000 smokers 4000 with + 4000 without diagnosis of mild to moderate psychiatric illness L

• Efficacy results provide a rationale for

choosing among medications

EAGLES Trial: Safety Outcome Composite neuropsychiatric event endpoint

Non-psychiatric cohort

Psychiatric cohort

Anthenelli. Lancet 2016

• No difference among drugs in rates of psychiatric adverse events in either stratum

FDA removed Black Box warning (Dec. 2016)

Optimizing Pharmacotherapy

• Combine drugs • Short- and long-acting NRT1

1 USPHS 2008. 2 Carpenter MJ et al. Drugs 2013. 3 Lindson-Hawley N et al. JAMA 2013.

0 2 4 6 8

10 12 14 16 18

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

ma

nico

tine

leve

l (ng

/mL)

Time post administration (min)

Cigarette (1-2 mg)

Nasal spray (1 mg)

Gum (4 mg)

Patch (21 mg)

Plasma Nicotine Levels Cigarettes vs. Nicotine Replacement Products

Nicotine Replacement Options Long-acting, slow onset nicotine delivery → skin patch

Short-acting, faster onset → gum, lozenge, inhaler, spray

+ Constant nicotine level to avoid withdrawal + Simplest to use - User has no control of dose

+ User controls dose - Nicotine blood levels fluctuate more - Many smokers do not use enough

Optimizing Pharmacotherapy

• Combine drugs • Short- and long-acting NRT1

• Drugs from different classes

1 USPHS 2008. 2 Carpenter MJ et al. Drugs 2013. 3 Lindson-Hawley N et al. JAMA 2013.

55 49

41

33

Week 12 (End of Treatment)

Week 24 Varenicline + NRT Varenicline + Placebo

OR: 1.85 CI: 1.19-

2.89 P=.007

OR: 1.98 CI: 1.25-

3.14 P=.004

53

37 31

43

28 25

0

10

20

30

40

50

60

Week 12 (End of

Treatment)

Week 26 Week 52 Prol

onge

d Sm

okin

g Ab

stin

ence

(%)

Varenicline + Bupropion Varenicline + Placebo

OR: 1.49 CI: 1.05-

2.12 P=.03 OR: 1.52

CI: 1.04-2.22

P=.03

OR: 1.39 CI: 0.93-

2.07 P=.11

Ebbert JO. JAMA. 2014;311(2):193-194. Koegelenberg C. JAMA 2014; 312:155.

Adding Bupropion or NRT to Varenicline: 2 RCTs Add bupropion Add nicotine patch

Selecting a Smoking Cessation Medication An Evidence-based Protocol

1st line

Varenicline OR combination NRT

2nd line

Bupropion OR single NRT product

If single agent is insufficient

Combine categories of FDA-approved drugs: Varenicline + NRT Varenicline + bupropion Bupropion + NRT

JACC December 25, 2018

OVERVIEW

Challenges in treating tobacco users

Which treatments work? Clinical Practice Guidelines Optimizing Pharmacotherapy

Practical strategies for office practice

Electronic cigarettes – risks and benefts

TREATING TOBACCO IN HEALTH CARE 2008 U.S. Public Health Service Guidelines – 5A’s

Routine advice to quit is effective

Brief counseling is more effective than advice only Evidence-based 5 step (5A) Guideline

ASK all patients about smoking ADVISE all smokers to quit ASSESS smoker’s readiness to quit ASSIST smokers to quit ARRANGE follow-up care

Reconsidering ASSESS:

Moving to an “Opt Out” model of treatment

If tobacco use is a chronic disease Don’t ask a if a smoker is ready to quit Just offer treatment:

“Quitting smoking can be hard, but there is good treatment and I can help you. Shall we give it a try?”

Treating Tobacco in the Office: A Practical Strategy 3 Step Model – Ask / Advise / Act

• ASK Do you ever smoke tobacco?

Are you exposed to smoke at home or at work?

• ADVISE Stopping smoking is key to stay (or become) healthy.

• ACT Offer treatment to all smokers

Prescribe pharmacotherapy

Connect to internal or community resources for behavioral support

ACT Free programs that are easy for patients to access

Telephone Quitline 1-800-QUIT NOW • Multi-session counseling by appointment: Convenient, private, free • IL Quitline offers free sample of nicotine patch, gum, lozenge, website • Make an active referral from your office

Smokefree.gov website • Sign up for

• SmokefreeTXT • Mobile app (quitSTART) • Web-based information

OVERVIEW

Challenges in treating tobacco users

Which treatments work? Clinical Practice Guidelines Optimizing Pharmacotherapy

Practical strategies for office practice

Electronic cigarettes – risks and benefits

Electronic Cigarettes A nicotine delivery device that looks like a cigarette

Nicotine + propylene glycol

or glycerin + flavoring

No tobacco burned→ Safer than cigarettes?

Not FDA regulated→ Many knowledge gaps

The devices are changing rapidly

Electronic Cigarettes

Net Public Health Impact Depends on 3 factors

Potential benefit Help more smokers to quit smoking (especially those unable to

quit with FDA-approved medications)

Potential risks Attract nonsmokers to vape→ develop nicotine dependence →

transition to cigarette smoking

Possible health risks of vaping Absolute (vs. nonsmoking) - youth Relative to combustible tobacco – adult smokers

E-Cigarettes - Summary of the Evidence 2018 National Academy of Science, Engineering and Medicine Report

Exposure: • E-cigarettes contain fewer (and lower levels)

of toxic substances than conventional cigarettes

Health Effects:

• While not without health risks, they are likely to be far less harmful than smoking combustible tobacco cigarettes

• Long-term health effects of e-cigarettes are not yet clear

E-Cigarettes – Public Health Effects 2018 National Academy of Science, Engineering and Medicine Report

• Using e-cigarettes may help adults quit smoking, but more research is needed

• Among youth, e-cigarette use increases the risk of initiating smoking

• Modelling results indicate that e-cigarettes will likely result in a net public health benefit

Participants 886 adult smokers (15 cig/d) attending British NHS Stop Smoking clinics No preference for NRT vs. e-cigarette to quit

Interventions Choice of type of NRT (combination recommended) – 3 mo. OR E-cigarette starter pack (refillable device + 1 bottle e-liquid) (All got 4 weekly counseling visits)

Among those who were quit at 1 year: 80% in e-cig group were still using e-cigs 9% in NRT group were still using NRT

Hajek P et al. N Engl J Med. Feb. 14, 2019.

Electronic Cigarettes What should you say to a smoker?

• Many unanswered questions about safety and efficacy

• They are likely less harmful than smoking combustible cigarettes

• Recommend FDA-approved safe, effective treatments first

• If these treatments are not effective or desired, then what?

• If using e-cigarettes, switch completely and stop smoking

• Urge patients using e-cigarettes to plan to quit e-cigs too because health effects of long-term use are not known.

Consistent with American College of Cardiology and American Cancer Society guidelines

JUUL Phenomenon

• Sleek high-tech design

• Better nicotine delivery

• Social media marketing

Monitoring the Future Study NEJM Dec. 2018 Annual cross-sectional school survey of US adolescents in grades 8-12 CAVEAT: Prevalence of smoking did not change and is at a historic low

Used in past 30 days

Sept. 5, 2019

Aug. 21, 2019

Aug. 16, 2019

CDC Health Advisory 8/30/19

Most in adolescents and young adults Symptoms Respiratory: cough, dyspnea, chest pain GI: nausea, vomiting, diarrhea Non-specific: fever, fatigue, weight loss

Onset: acute (several days) to subacute (weeks) Exam: fever, tachycardia Lab: ↑WBC; No infectious etiology identified after work-up

CXR: bilateral infiltrates

Clinical course Many required

supplemental O2

Some needed mechanical ventilation

Antimicrobials do not appear to be helpful

Possible response to corticosteroids

NYTimes 8/30/19 CDC Advisory – 8/30/19

Exposures All used e-cigarette products

(different devices) a few days to weeks before symptoms started

Most reported using e-cigarettes containing cannabinoids (THC, CBD)

Some used e-liquids not purchased from stores

No single substance or product is associated with the illness

Products found to contain vitamin E acetate

– NY Dept of Health

NYT 10/3/19

September 24, 2019 805 cases

in 46 states + USVI

12 deaths

October 11, 2019 1299 cases

49 states + DC + USVI

26 deaths

CDC Updates

Demographics 70% male 80% <35 yo (median = 24 yo)

Exposures 76% reported vaping THC vaping 58% reported vaping nicotine 32% vaped only THC 13% vaped only nicotine

MMWR 10/11/19

Why is this appearing now? New contaminant in the supply chain of e-cigarettes? Clustering of cases E-cigs have been sold for years, including to youths, without

these cases appearing Strong association with THC, home-made or street-bought

e-liquids that may have new contaminants

My hypothesis: Most likely due to illicit products, not to commercial e-cigarette products…but we don’t know for sure

Why is this appearing now? New recognition of a complication of vaping? Was this a rare event that was not recognized? Could cases appear now because newer e-cigs are more

addictive and increased daily vaping prevalence by youths?

A combination of factors? Does vaping impair lung immune mechanisms, making lungs

more susceptible to a 2nd insult (infection), increasing risk of ARDS?

CDC Recommendations for the Public E-cigarettes should not be used by nonsmokers of any age. What about smokers or current e-cigarette users?

“While investigation is ongoing, if you are concerned about these specific health risks, consider refraining from using e-cigarettes.”

Current smokers: use FDA approved cessation aids. Current e-cigarette users:

“If you are an adult who used e-cigarettes containing nicotine to quit cigarette smoking, do not return to smoking cigarettes.”

Don’t use street-acquired products, especially THC Don’t add substances to cartridges or re-use cartridges Monitor yourself for pulmonary symptoms

MI, NY, RI, WA All flavored e-cigarettes except tobacco and mint/menthol

MA All e-cigarettes (including tobacco flavor) – for 4 months

SF Ban sales and distribution of all e-cigarettes

Cautions Effects of vaping bans are unclear and controversial Will they ↓ or ↑ risk of acute lung injury? Will they ↓ youth vaping rates? Will they ↓ adult cessation rates?

Let’s not “throw the baby out with the bath water”

1 in 2 smokers still die of tobacco related disease Many smokers repeatedly fail to quit with existing treatments E-cigarettes can help smokers to quit and are less harmful

than continuing to smoke

NEXT BEST STEPS Treating smoking = chronic disease management

Use combinations of treatments Drugs + counseling Combine drugs

Use the systems being built to help you Quitline (1-800-QUIT NOW) www.Smokefree.gov

Keep an eye on the CDC and FDA websites as the investigation of acute vaping illness proceeds