Primary Care Conference Primary Care Conference Case Presentation: A New Case Presentation: A New

Smoking Cessation Treatment Smoking Cessation Treatment OptionOption

25 October 200625 October 2006

Douglas E. Jorenby, Ph.D.Douglas E. Jorenby, Ph.D.

DisclosuresDisclosures

Research support from Pfizer, Nabi Research support from Pfizer, Nabi Biopharmaceuticals, NIDABiopharmaceuticals, NIDA

Consulting and educational honoraria Consulting and educational honoraria from Nabi Biopharmaceuticals, from Nabi Biopharmaceuticals, Veterans’ AdministrationVeterans’ Administration

Learning ObjectivesLearning Objectives

Understand the mechanism of action Understand the mechanism of action of varenicline for smoking cessationof varenicline for smoking cessation

Be informed regarding the pros and Be informed regarding the pros and cons of this treatmentcons of this treatment

Apply evidence-based smoking Apply evidence-based smoking cessation treatments in a patient cessation treatments in a patient with multiple complicating factorswith multiple complicating factors

Case HistoryCase History

Caucasian male in his late 40sCaucasian male in his late 40s Currently smoking 15 cpdCurrently smoking 15 cpd Daily smoker for over 30 yearsDaily smoker for over 30 years Longest period of cessation = 6 mos.Longest period of cessation = 6 mos. Failed “cold turkey”Failed “cold turkey” Not using other forms of tobacco Not using other forms of tobacco

SCPC AssessmentsSCPC Assessments

BP 140/82BP 140/82 CO = 18 ppmCO = 18 ppm FVC = 3.91 l (79%)FVC = 3.91 l (79%) FEV1 = 3.26 l (82%)FEV1 = 3.26 l (82%) FEF25-75 = 3.75 l/s (96%)FEF25-75 = 3.75 l/s (96%)

Complicating FactorsComplicating Factors

Seizure disorderSeizure disorder Sleep apneaSleep apnea Visual impairmentVisual impairment Caffeine useCaffeine use Alcohol useAlcohol use

Things Go Better With Things Go Better With DopamineDopamine

NicotineNicotine BupropionBupropion CytisineCytisine VareniclineVarenicline

The The αα44ββ2 Receptor Subtype2 Receptor Subtype

Key to the rewarding effects of Key to the rewarding effects of nicotinenicotine

Modulates dopamine releaseModulates dopamine release Varenicline has 35-60% of the Varenicline has 35-60% of the

agonist effectagonist effect Affinity is higher than for nicotineAffinity is higher than for nicotine

Randomized Controlled TrialRandomized Controlled Trial

Phase 3 placebo-controlled Phase 3 placebo-controlled comparisoncomparison

1.0 mg twice daily (n=344)1.0 mg twice daily (n=344) 150 mg bupropion SR twice daily 150 mg bupropion SR twice daily

(n=342)(n=342) Placebo (n=341)Placebo (n=341)

Participant CharacteristicsParticipant Characteristics

VareniclinVareniclinee

Bupropion Bupropion SRSR PlaceboPlacebo

% Male% Male 55.2 60.2 58.1

AgeAge 44.6 42.9 42.3

% White% White 85.5 82.7 85

YearsYears 27.1 25.4 24.4

CPDCPD 22.5 21.8 21.5

FTNDFTND 5.39 5.39 5.16

Point Prevalence OutcomePoint Prevalence Outcome

Jorenby DE, et al. JAMA. 2006;296:56-63.

Rates of DiscontinuationRates of Discontinuation

0

50

100

150

200

250

300

350

Varenicline Bupropion SR Placebo

RandomizedDiscontinuedAE

Jorenby DE, et al. JAMA. 2006;296:56-63.

Nausea As AENausea As AE

0

5

10

15

20

25

30

VareniclineBupropion SRPlacebo

Jorenby DE, et al. JAMA. 2006;296:56-63.

Oncken C, et al. Arch Intern Med. 2006;166:1571-1577.

Oncken C, et al. Arch Intern Med. 2006;166:1571-1577.

Point Prevalence Outcome Point Prevalence Outcome ReplicationReplication

Gonzales D, et al. JAMA. 2006;296:47-55.

Dosing RegimenDosing Regimen

0.5 mg in the morning for 3 days, 0.5 mg in the morning for 3 days, thenthen

0.5 mg twice a day for 4 days, then0.5 mg twice a day for 4 days, then 1 mg twice a day (target quit date)1 mg twice a day (target quit date) Continue for 3-6 monthsContinue for 3-6 months

Dose & Titration Effects On Dose & Titration Effects On NauseaNausea

0

5

10

15

20

25

30

35

40

45

1.0 NT1.0 T2.0 NT2.0 TPlacebo

Oncken C, et al. Arch Intern Med. 2006;166:1571-1577.

A Matter Of ScaleA Matter Of Scale

Bupropion SRBupropion SR

Hurt et al. (1997)Hurt et al. (1997) Jorenby et al. (1999)Jorenby et al. (1999)

N = 1,508N = 1,508

VareniclineVarenicline Gonzales et al. Gonzales et al.

(2006)(2006) Jorenby et al. (2006)Jorenby et al. (2006) Tonstad et al. (2006)Tonstad et al. (2006) Nides et al. (2006)Nides et al. (2006) Oncken et al. (2006)Oncken et al. (2006)

N = 5,265N = 5,265

Case OutcomeCase Outcome

Medication well-toleratedMedication well-tolerated Attended SCPC support group for 4 Attended SCPC support group for 4

weeksweeks Reported no withdrawal symptoms (?!)Reported no withdrawal symptoms (?!) Smoke-freeSmoke-free Follow-up at 6 monthsFollow-up at 6 months Repeat PFT at 12 monthsRepeat PFT at 12 months