1 ctri webinar: combination medication effectiveness june 9, 2010 stevens s. smith, ph.d. megan e....
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CTRI Webinar:Combination Medication
Effectiveness
June 9, 2010
Stevens S. Smith, Ph.D.Megan E. Piper, Ph.D.Center for Tobacco Research & InterventionUW School of Medicine and Public Health
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Combination Medication Effectiveness
Rationale PHS Guideline medication recommendations Overview of UW-CTRI Transdisciplinary Tobacco
Use Research Center (TTURC2) studies TTURC2 Effectiveness Study in primary care clinics TTURC2 Randomized Clinical Trial (Efficacy Study) Conclusions Questions and answers
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Rationale
Tobacco dependence – chronic, relapsing disease Most smokers want to quit; about 40% try each year 70% visit a primary care physician each year Effective treatments exist 2008 Public Health Service Guideline provides
specific evidence-based treatment recommendations How do we optimize cessation success with
medications?
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The "5 A's" Model for Treating Tobacco Use and Dependence - 2008
ASK
Do you currently use
tobacco?
ASSESS
Have you recently quit?
Any challenges?
ASSIST
Provide appropriate tobacco dependence
treatment
ASSIST
Intervene to increase motivation
to quit
ASSIST
Provide relapse prevention
ASSIST
Encourage continuedabstinence
YES
NO
YES NONO
YES
ADVISE to quit
ASK
Have you ever used tobacco?
YES NO
ARRANGE FOLLOW-UP
ASSESSAre you willing to quit now?
MedicationAnd
Counseling
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Guideline Recommendation:FDA-Approved Cessation Medications
Clinicians should encourage medication for all patients attempting to quit smoking
– EXCEPT when medically contraindicated– EXCEPT when there is insufficient evidence of effectiveness (i.e.,
pregnant women, smokeless tobacco users, light smokers and adolescents)
The combination of counseling and medication is more effective for smoking cessation than either medication or counseling alone. Therefore, whenever feasible and appropriate, both counseling and medication should be provided to patients trying to quit smoking.
Guideline Recommendation:FDA-Approved Cessation Medications
Seven first-line medications (5 nicotine and 2 non-nicotine) reliably increase long-term smoking abstinence rates- Bupropion SR - Nicotine gum*
- Nicotine lozenge* - Nicotine nasal spray
- Nicotine inhaler - Nicotine patch*
- Varenicline
Clinicians should also consider the use of certain combinations of medications identified as effective in this Guideline
7 *Available without a prescription
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MedicationNumberof arms
Estimatedodds ratio(95% C.I.)
Estimatedabstinence rate
(95% C.I.)
Nicotine Patch 321.9
(1.7 - 2.2)23.4%
(21.3 – 25.8)
Bupropion SR 262.0
(1.8 – 2.2)24.2%
(22.2 – 26.4)
Varenicline 53.1
(2.5 – 3.8)33.2%
(28.9 - 37.8)
Patch (>14 wks)+ NRT (gum or spray)
33.6
(2.5 – 5.2)36.5%
(28.6 – 45.3)
Patch + Bupropion SR 32.5
(1.9 – 3.4)28.9%
(23.5 – 35.1)
Selected Medication Options:Monotherapy and Combination Therapy
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Relative Efficacy
MedicationNumber of arms
Estimated odds ratio (95% C. I.)
Nicotine Patch (reference group) 32 1.0
Varenicline (2 mg/day) 51.6
(1.3, 2.0)
Patch (>14 weeks) + NRT (gum or spray)
31.9
(1.3, 2.7)
Patch + Bupropion SR 31.3
(1.0, 1.8)
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2008 PHS Guideline: Combination Medication Recommendation
Recommendation: Certain combinations of first-line medications have been shown to be effective smoking cessation treatments. Therefore, clinicians should consider using these combinations of medications with their patients who are willing to quit. Effective combination medications are: * Long-term (> 14 weeks) nicotine patch + other NRT
(gum and spray)* The nicotine patch + the nicotine inhaler * The nicotine patch + bupropion SR.
(Strength of Evidence = A)
UW-CTRI Transdisciplinary Tobacco Use Research Center (TTURC2) Studies
Funded by NIH Two independent samples of smokers attempting cessation Effectiveness study (Stevens will discuss) Efficacy study (Megan will discuss)
Five active pharmacotherapy treatments in each study: Nicotine patch Nicotine lozenge Bupropion SR Nicotine patch + Nicotine lozenge Bupropion SR + Nicotine lozenge Placebo (Efficacy study only)
TTURC2 Studies
• Effectiveness Study – 1346 smokers recruited in 12 primary care clinics– Enrollment offered during regular primary care visits
• Efficacy Study (Randomized Clinical Trial)– 1504 smokers– Participants - smokers motivated to quit recruited from
community – In-depth multi-method assessments of their smoking, physical
health, mental health and life context – Agreed to be followed up for at least 3 years
Effectiveness Study
Bupropion Nicotine Lozenge
Nicotine Patch
Bupropion + Lozenge
Patch+ Lozenge
RandomizationN = 1346
N = 256 N = 261 N = 282 N = 268 N = 279
Primary care patients presentingto 12 primary care clinics
Effectiveness Study: Treatment Model
• Clinic Medical Assistant Asks, Assesses and Offers a smoking cessation study
• Physician encourages and clears for medications• Research staff enrolls, provides Rx and quitline
referral• Clinic pharmacist dispenses meds with instructions• Quitline staff provide 4 phone counseling sessions
Effectiveness Study: Participants
1346 smokers – Mean age = 44.3, SD = 12.1– 56% female– 87% Caucasian
Representative of the demographics of the population of smokers in the clinics
Total N=1346 Bupropion
(N=256)
Lozenge
(N=261)
Patch
(N=282)
Bupropion + Lozenge
(N=268)
Patch + Lozenge
(N=279)
6 Month
% Abstinent16.8% 19.9% 17.7% 29.9% 26.9%
OR – Bup+Loz
as reference.46
p<.001
.56
p<.01
.48
p<.001- -
OR – Patch+Loz
as reference.54
p<.01
.67
p=.06
.56
p<.01- -
Effectiveness Study: Cessation Rates (% Abstinent at 6 Months)
Figure 2. Abstinence rates
0
10
20
30
40
50
60
70
Week 1 Week 8 Six Months
Post-Quit Study Endpoints
Per
cen
t A
bst
inen
t
Bupropion
Lozenge
Patch
Bupropion+Lozenge
Patch+Lozenge
Effectiveness Study: Cessation Rates
Efficacy Study CONSORT Figure
N = 8526Expressed interest
n = 1418Declined
n = 2010Unreachable
n = 2027Failed screen
n = 3153Passed phone screen
n = 1331Withdrew
n = 1504Randomized
n = 318Excluded
Lozengen = 260
Patchn = 261
Bupropion SR
n = 266
Patch +Lozengen = 267
Bupropion SR + Lozenge
n = 261
Placebon = 189
Efficacy Study Participants
N = 1504 (628 men, 876 women) Ethnicity
– 1258 (83.9%) White – 204 (13.6%) African-American – 42 (2.8%) parents of Hispanic origin
21.9% had a 4-year college degree Mean age = 44.67 (SD = 11.08) Mean cigs. smoked/day = 21.43 (SD = 8.93) Mean number of quit attempts = 5.72 (SD = 9.65)
Efficacy Study Treatments
All participants received 6 brief (10-20 min) individual counseling sessions
Bupropion SR – 150 mg bid for 9 weeks
Nicotine patch – 24-hour patch; 21, 14, and 7mg; titrated down over 8 weeks
post-quit Nicotine lozenge
– 2 or 4 mg, based on dependence level per package instructions, for 12 weeks post-quit
Efficacy Study Outcomes: % Abstinent for Active Conditions vs. Placebo
Placebo Bupropion Lozenge Patch Bupropion + Lozenge
Patch + Lozenge
Initial cessation
65.5 78.9OR = 2.04
77.2OR = 1.91
86.3OR = 3.14
82.0OR = 2.40
89.8OR = 4.73
8 weeks 30.2 40.2OR = 1.55
40.4OR = 1.57
44.7OR = 1.87
50.4OR = 2.35
53.6OR = 2.67
6 months 22.2 31.8OR = 1.63
33.5OR = 1.76
34.4OR = 1.83
33.2OR = 1.74
40.1OR = 2.34
= p < .05 = p < .005
Efficacy Study: Latency to Relapse
Placebo
Lozenge/Bupropion
Patch + Lozenge
Patch/BupropionBupropion + Lozenge+ Lozenge
Efficacy Study Adverse Events
Placebo (n = 189)
Bupropion (n = 262)
Lozenge (n = 260)
Patch
(n = 264)
Bupropion + Lozenge (n = 267)
Patch + Lozenge (n = 262)
Nausea 16 (4.4) 20 (3.8) 44 (7.8) 25 (4.3) 33 (5.0) 55 (7.9)
Skin irritation 10 (2.7) 14 (2.7) 3 (1.0) 86 (14.7) 14 (2.1) 62 (8.9)
Mouth/throat irritation 12 (3.3) 11 (2.1) 38 (6.7) 11 (1.9) 15 (2.3) 40 (5.7)
Alteration of taste 2 (1.0) 8 (1.5) 1 (0.2) 0 (0.0) 9 (1.4) 0 (0.0)
Sleep disturbance/ abnormal dreams
20 (5.6) 88 (16.8) 18 (3.2) 66 (11.3) 69 (10.6) 63 (9.0)
Hiccups 1 (0.3) 0 (0.0) 35 (6.2) 0 (0.0) 7 (1.1) 22 (3.2)
Headaches 24 (6.7) 23 (4.4) 29 (5.1) 26 (4.4) 30 (4.6) 34 (4.9)
Total adverse events 359 524 566 585 654 697
Effectiveness Study Milwaukee
n=815
Efficacy Study Milwaukee
n=883
AgeGender (%female)
44.1 (11.8)55%
45.5 (10.7)56.7%
Race/Ethnicity % Caucasian% Afr.Amer.% Other
83%13.9%3.0%
75.9%21.1%2.9%
Cigarettes/dayFTND
19.7 (8.7)5.0 (2.1)
21.9 (9.3)5.5 (2.1)
Household income<$35,000$35-49,999>$50,000
35.5%20.5%44%
40%19.3%40.7%
Education <HS HS
>HS
13.7%46.6%39.6%
8.1%25.3%66.5%
Demographic Comparisons for Both Studies
Conclusions
The combination therapies (bupropion + nicotine lozenge and nicotine patch + nicotine lozenge) produced the highest long-term abstinence rates in the Effectiveness Study
The combination of nicotine patch + lozenge produced the highest long-term abstinence rates in the Efficacy Study
Efficacy Study data supports safety and patient acceptance of combination NRT
These results agree with 2008 PHS Guideline that both single and combination pharmacotherapies are effective, with combination NRT therapy being particularly effective.
The nicotine patch remains a highly efficacious pharmacotherapy for helping smokers quit.
For women, combination therapy produced the highest long-term abstinence rates relative to monotherapies.
For African-American smokers, combination therapy did not appear to have any added benefit over and above monotherapies.
For smokers with <high school education, combination therapy produced significantly higher abstinence rates relative to monotherapies.
Conclusions
Acknowledgements
These studies were conducted at the University of Wisconsin and supported by NIH Grant # P50-DA0197. Dr. Piper was supported by an Institutional Clinical and Translational Science Award (UW-Madison; KL2 Grant # 1KL2RR025012-01).
Medication was provided to patients at no cost under a research agreement with GlaxoSmithKline.
Tanya R. Schlam, Ph.D. Michael C. Fiore, M.D., M.P.H. Douglas E. Jorenby, Ph.D. David Fraser, M.S. Timothy B. Baker, Ph.D. Madison and Milwaukee Study Staff