Treating Tobacco Use:

Transcription

1 Treating Tobacco Use: Optimizing for the Best Outcomes Nancy Rigotti, MD Director, MGH Tobacco Research and Treatment Center Professor of Medicine, Harvard Medical School Primary Care Internal Medicine CME 2018

2 Disclosures Nancy Rigotti, MD Research grants, NIH Royalties, UpToDate, Inc. Unpaid consultant, Pfizer, Inc. Paid Consultant, Achieve Life Sciences

3 What s new in tobacco U.S. Smoking Rates Are On The Decline, but There s a Catch

4 OVERVIEW Challenges in Treating Tobacco Users What Treatments Work? U.S. Clinical Practice Guidelines (2008) Optimizing Pharmacotherapy Treating Tobacco as a Chronic Disease Electronic cigarettes

5 WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. 38 million U.S. adults still smoke (15% in 2016) We ve left vulnerable populations behind Less educated, lower incomes Mental illness Other substance use disorders Homeless or incarcerated LGBT MMWR 2012;61:889. MMWR 2014; 63:1108. MMWR 2016;65:1205

6 WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. 38 million U.S. adults still smoke (15% in 2016) Patterns of tobacco use are changing More light smokers (<10 cig/day) Many non-daily smokers (22%) Multiple product use (40% use more than 1 product) Small cigars, roll your own (cheaper than cigarettes)

7 WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. 37 million U.S. adults still smoke Cessation reduces mortality

8 Effect of Smoking Cessation on Survival to 80 Years of Age, By Age at the Time of Quitting Smoking Jha P et al. N Engl J Med 2013;368:341

9 WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. 37 million people in U.S. still smoke Cessation reduces mortality Even after chronic disease develops 1 Even after age 65 2 Even when weight gain occurs 3 It s never too early or too late to quit 1 Critchley et al. JAMA 2003;290:86; 2 Gellert et al. Arch Intern Med 2012; 172:837; 3 Nu et al. NEJM 2018; 379:623.

10 WHY TREATING TOBACCO USE MATTERS #1 preventable cause of death in the U.S. 37 million people in U.S. still smoke Cessation reduces mortality Tobacco treatment delivered in practice works

11 A Case 55 yo man with HTN, BMI 30, depression (stable SSRI) Smokes 20 cigarettes/day since 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 cut down but couldn t quit Chantix? I heard that drug is dangerous! What do you think about the electronic cigarette?

12 QUESTIONS What s an electronic cigarette? Has he really tried everything? Is varenicline (Chantix) really risky? What s your next step?

13 QUITTING IN PERSPECTIVE National Health Interview Survey % of current smokers want to quit 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 MMWR January 2017;65:1457

14 OVERVIEW Challenges in Treating Tobacco Users What Treatments Work? U.S. Clinical Practice Guidelines (2008) Optimizing Pharmacotherapy Treating Tobacco as a Chronic Disease Electronic cigarettes

15 SMOKING CESSATION METHODS 2008 US Public Health Service Guideline Effective treatments exist Counseling (in-person, group, telephone) Pharmacotherapy Combination is better than either one alone More is better but even brief intervention works Endorsed by 2015 US Preventive Services Task Force

16 PHARMACOTHERAPY 1 st Line 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 ~ double quit rate vs. placebo

17 Goal = nicotine withdrawal All products ~ equally effective

18 BUPROPION SR Atypical antidepressant - dopamine in CNS Increases cessation rate independent of its antidepressant effect Clinical use Start 1 week before quit day (150 mg qd bid) Treat for 3-6 months Increases seizure risk (Risk <0.1%)

19 NH VARENICLINE N N 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

20 VARENICLINE Clinical use Start 1-4 weeks before quit day Dose ramps up over 1 week to avoid nausea (to 1 mg bid) Treat for 3-6 months Most common side effects nausea, vivid dreams

21 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 DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm htm

22 VARENICLINE SAFETY The dilemma Stopping smoking nicotine withdrawal symptoms (depressed mood, anxiety, and irritability) When these symptoms occur in a smoker who is stopping smoking on varenicline, did the drug or did quitting smoking cause the symptom? Case reports can not answer the question Meta-analysis of 39 double-blind RCTs of varenicline no excess of depression or suicidal thoughts But few had patients with mental illness (Thomas KH, BMJ 2015)

23 EAGLES Randomized Controlled Trial Nicotine patch vs. bupropion vs. varenicline vs. placebo 8000 smokers (4000 with without psychiatric diagnosis) Lancet 2016

24 EAGLES: Efficacy and Safety Outcomes Continuous abstinence (Efficacy)

25 EAGLES: Efficacy and Safety Outcomes Continuous abstinence (Efficacy) Composite neuropsychiatric event endpoint (Safety)

26 VARENICLINE SAFETY Bottom Line Sum of the evidence does not suggest that varenicline is more hazardous than other cessation medication, even in patients with comorbid psychiatric illness. FDA removed the Black Box warning (Dec. 2016)

27 Optimizing Pharmacotherapy Combine drugs Short- and long-acting NRT 1 1 USPHS Carpenter MJ et al. Drugs Lindson-Hawley N et al. JAMA 2013.

28 PLASMA NICOTINE LEVELS Cigarettes vs. Nicotine Replacement Products Plasma nicotine level (ng/ml) Cigarette (1-2 mg) Nasal spray (1 mg) Gum (4 mg) Patch (21 mg) Time post administration (min)

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

30 Current Pharmacotherapy Options Cochrane meta-analysis, 2013 (JAMA. 2014;311: ) Drug vs. Placebo Odds Ratio # of Studies (95 % Credible (Direct Interval) Comparisons) Nicotine Replacement (NRT) 1.84 (1.71, 1.99) 119 Bupropion 1.82 (1.6, 2.06) 36 Varenicline 2.88 (2.4, 3.47) 15 Combination NRT 2.73 (2.07, 3.65) 2 Favors placebo Favors active drug Posterior Median Odds

31 Optimizing Pharmacotherapy Combine drugs Short- and long-acting NRT 1 Drugs from different classes 1 USPHS Carpenter MJ et al. Drugs Lindson-Hawley N et al. JAMA 2013.

32 Combining Drugs Across Classes Is there a Tier 3? 2 placebo controlled randomized trials Each started with varenicline 1 added bupropion (vs. placebo) 1 added nicotine patch (vs. placebo)

33 Adding Bupropion or NRT to Varenicline Prolonged Smoking Abstinence (%) OR: 1.49 CI: P= Add bupropion OR: 1.52 CI: P= OR: 1.39 CI: P= OR: 1.85 CI: P= Add nicotine patch OR: 1.98 CI: P= Week 12 (End of Treatment) Week 26 Week 52 Week 12 (End of Treatment) Week 24 Varenicline + Bupropion Varenicline + Placebo Varenicline + NRT Varenicline + Placebo Ebbert JO. JAMA. 2014;311(2): Koegelenberg C. JAMA 2014; 312:155.

34 Optimizing Pharmacotherapy Combine drugs Short- and long-acting NRT 1 Drugs from different classes Start patch 2 weeks before quit day 2 1 USPHS Carpenter MJ et al. Drugs 2013.

35 Optimizing Pharmacotherapy Combine drugs Short- and long-acting NRT 1 Drugs from different classes Start patch 2 weeks before quit day 2 Reduce to quit (gradual reduction) 3 1 USPHS Carpenter MJ et al. Drugs Ebbert JO et al. JAMA 2015

36 JAMA 2015 PARTICIPANTS Smokers who want to quit in the next 3 months but are not willing to set a quit date within 1 month CONDITIONS Randomized to varenicline vs PCB for 24 weeks OUTCOMES Abstinence at 24, 52 weeks

37 Optimizing Pharmacotherapy Combine drugs Short- and long-acting NRT 1 Drugs from different classes Start patch 2 weeks before quit day 2 Reduce to quit (gradual reduction) 3 Treat longer to prevent relapse 1 1 USPHS Carpenter MJ et al. Drugs Ebbert JO et al. JAMA 2015.

38 OVERVIEW Challenges in Treating Tobacco Users What Treatments Work? U.S. Clinical Practice Guidelines (2008) Optimizing Pharmacotherapy Treating Tobacco as a Chronic Disease Electronic cigarettes

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

40 TREATING TOBACCO IN THE OFFICE U.S. Public Health Service Guidelines 5A s ASK ADVISE ASSESS ASSIST ARRANGE Done by office staff (vital sign) Core clinician role Hand off to others?

41 ASK About smoking Do you ever smoke tobacco? About secondhand smoke exposure Do you live with a smoker? Is smoking ever allowed in your home or car?

42 Reconsidering ASSESS 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. Would you like to try? ASSIST = offer meds and refer for support

43 REFER Free programs that are easy to access Telephone Quitline Proactive multisession counseling Convenient, private, free Many also offer free NRT sample, text messages, web support QUIT NOW Active referral from your office (fax or e-refer)

44 QUITWORKS system Staff fax referral form to Quit line Quit line calls smoker to offer counseling + NRT Quit line gives doctor feedback on patient

45 REFER Free programs that are easy to access Smokefree.gov website Sign up for free text messages (SmokefreeTXT) QuitGuide (mobile phone app) Web-based information about quitting Becomeanex.org website Support from experts Access to online community for support

46 TREATING TOBACCO IN THE OFFICE 3 Step Model : Ask / Assist / Refer ASK ASSIST Done by office staff (vital sign) Core clinician role Offer treatment + prescribe REFER to internal/community resource Fax or erefer to Quitline Refer to

47 OVERVIEW Challenges in Treating Tobacco Users What Treatments Work? U.S. Clinical Practice Guidelines (2008) Optimizing Pharmacotherapy Treating Tobacco as a Chronic Disease Electronic cigarettes

48 What is this woman doing? No, she s not smoking a cigarette. She s vaping.

49 ELECTRONIC CIGARETTE A nicotine delivery device that looks like a cigarette Invented in China ~ 2003 Rapid growth in US sales started ~ 2011 Not FDA regulated until August 2016 Nicotine + propyline glycol + flavoring The products are evolving to look less like cigarettes

50 cigalikes Refillable

51 ELECTRONIC CIGARETTES Many Questions, Few Answers How much nicotine do they actually deliver? Who is using them?

52 Prevalence of e-cigarette use by smoking status - US adults, 2014

53 ELECTRONIC CIGARETTES Many Questions, Few Answers How much nicotine do they actually deliver? Who is using them? Why are they using them? To quit smoking To reduce health risk of smoking Use where they can t smoke cigarettes

54 ELECTRONIC CIGARETTES Many Questions, Few Answers Will they help people stop smoking? Randomized controlled trial 1 good randomized controlled trial so far (Bullen C et al, Lancet, 2013) E-cig vs. nicotine patch in smokers who wanted to quit Both treatments had similar low quit rates

55 ELECTRONIC CIGARETTES Many Questions, Few Answers Will they appeal to youth who would not otherwise have started to smoke but then transition to cigarettes? Gateway hypothesis

56 Past 30 day tobacco product use by high school students U.S. National Youth Tobacco Survey, MMWR 2016:65:361-7

57 EVIDENCE SUMMARY National Academy of Science Report 2018 E-cigarettes contain fewer (and lower levels) of toxic substances than conventional cigarettes While not without health risks, they are likely to be far less harmful than combustible tobacco cigarettes The long-term health effects of e-cigarettes are not yet clear

58 EVIDENCE SUMMARY National Academy of Science Report 2018 Using e-cigarettes may help adults quit smoking combustible tobacco cigarettes, but more research is needed Among youth, e-cigarette use increases the risk of initiating smoking of combustible tobacco cigarettes Modelling results indicate that e-cigarettes will likely result in a net public health benefit

59 ELECTRONIC CIGARETTES Question for you What should you tell a smoker who asks? Many unanswered questions about safety, efficacy for quitting They are not FDA approved Less harmful than smoking combustible cigarettes Recommend trying FDA-approved safe and effective treatment Don t recommend but don t discourage if smokers insist If using, switch completely to e-cigarettes and avoid flavors Encourage patients using e-cigarettes to plan to quit them too

60 The JUUL Phenomenon Sleek high-tech design Better nicotine delivery Social media marketing

61 Instagram twitter Magazine ad

62 JUUL = now the market leader Source: Nielsen Total US xaoc/convenience Database & Wells Fargo Securities, LLC

63 BEYOND ELECTRONIC CIGARETTES? iqos A heat-not-burn-cigarette

64 A Case: Revisited What s an electronic cigarette? Has he really tried everything? Combination NRT to achieve adequate dose Combine drugs: NRT + bupropion Varenicline Behavioral support key to bolster self-confidence Candidate for lung cancer CT screening

65 SUMMARY Treating smoking = chronic disease management Use combinations Drugs + counseling Combine drugs Use the systems being built to help you Quitline (1-800-QUIT NOW) New harm reduction products are here to stay

66 Take Home Message Treat Tobacco Use Like a Chronic Disease It needs long-term management and as much of your attention as treating hypertension and diabetes