- Professor Riccardo Polosa is the director of the Institute of Internal Medicine and Clinical Immunology at the University of Catania. He has conducted research on e-cigarettes and has received funding from pharmaceutical companies and the e-cigarette industry. - He presented on clinical studies that have evaluated the effects of e-cigarettes on withdrawal symptoms and cravings. Studies have found that e-cigarettes can reduce withdrawal symptoms and cravings, though the effect on cravings depends more on the ritual than nicotine. - Larger randomized controlled trials have also found that e-cigarettes help smokers reduce or quit smoking compared to other nicotine replacement therapies or no aid. Success rates were

1. Prof Riccardo Polosa
Director
Institute of Internal Medicine and Clinical Immunology
University of Catania

2. Conflict of interest – Riccardo Polosa
• Professor of Internal Medicine supported by the University of Catania, Italy
• Scientific advisor for LIAF (Italian acronym for Italian Anti Smoking League)
• Research grant
•Pharma industry (Pfizer, GSK, Novartis)
•E-cig industry (Arbi Group Srl)
• Consultancy role
•Global Health Alliance for treatment of tobacco dependence
•Pfizer
•ECITA (Electronic Cigarette Industry Trade Association, in the UK) Lectures fees from E-cig industry and trade associations (including FIVAPE in France and FIESEL in Italy) were entirely donated to vaper advocacy organizations

3. Clinical Studies of e-Cigarettes:
What we have learned so far
Prof. Riccardo Polosa
Institute of Internal Medicine
Centre for the Prevention and Cure of Tabagism
University of Catania - ITALY
E-Cigarette Summit | 13 Nov 2014 | London

4. •RCTs
–Subjective effects
–Physiological effects
•Uncontrolled studies
–Subjective effects
–Physiological effects
•Laboratory studies
–Subjective effects
–Physiological effects
OUTLINE

5. Bullen C, et al. Tob Control. 2010;19(2):98-103.
Reduction in tobacco withdrawal symptoms:
Desire to smoke

6. Bullen C, et al. Tob Control. 2010;19(2):98-103.
2.1 ng/ml
Serum Nicotine Levels
Reduction in tobacco withdrawal symptoms: Desire to smoke

7. Comparisons of change in desire to smoke
and other withdrawal symptoms from baseline
between 0 and 16 mg nicotine e-cigs
Bullen C, et al. Tob Control. 2010;19(2):98-103.

8. Vansickel AR, et al. Cancer Epidemiol Biomarkers Prev. 2010;19:1945-53
Reduction in tobacco withdrawal symptoms:
QSU and craving ratings

9. Important factors when interpreting EC data
Findings with the product under investigation
cannot be extended to other models

10. Craving control – 2° generation ECs
#
*
#
Adriaens K et al. IJERPH 2014
8 weeks

11. Craving control – 2° generation ECs
#
*
#
Adriaens K et al. IJERPH 2014
8 weeks

12. Craving control – 2° generation ECs
#
*
#
Adriaens K et al. IJERPH 2014
8 weeks

13. Working Memory (Trigram WM Task)
*
*
*
* p < 0.01 compared to nicotine

14. Learning Points
•EC can reduce craving and (to a lesser extent) nicotine withdrawal symptoms
•Effect on craving more “ritual” dependent
•Effect on withdrawal symptoms more nicotine dependent
•Nicotine EC can prevent the memory decrement

15. Randomised Controlled Trials
•‘Categoria’ 24mg nicotine EC vs. 18mg nicotine EC vs. no nicotine EC
•300 smokers (unwilling to quit)
•1 year abstinence rates: 13%, 9% and 4%
•good tolerability
(Caponnetto et al. Plos One 2013)
•‘Elusion’ 16mg nicotine EC vs. nicotine patch vs. no nicotine EC
•657 smokers (motivated to quit)
•6 month abstinence rates: 7.3%, 5.8% and 4.1%
•good tolerability
(Bullen et al. Lancet 2013)

16. STUDY ASSESSMENTS
Procedure BL
Visit
Wk2 Wk4 Wk6 Wk8 Wk10 Wk12 Wk24 Wk52
Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Visit 8 Visit 9
Informed consent
X
Sociodemografic factors X
Medical history X
Drug history X
Physical examination X X X X
Vital signs – HR & BP X X X X X X X X X
Weight - Kg X X X X
Smoking Hx X
BDI and BAI X
FTND X
S
M
O
K
E
C
H
A
R
T
eCO X X X X X X X X X
GN-SBQ X
NO and spirometry X X X X X X
Saliva collection for cotinine X X
Give Study Diary X X X X X X
Collect Study Diary X X X X X X
Craving/VAS X X X X X X X X X
MNWS (past 2 weeks) X X X X X X X X X
MNWS (past 24 hrs) X X X X X X X X X
Adverse events X X X X X X X X X
E-cig training
and dispense of E-cig kit
X
Dispense study cartridges X X X X X X
Cartridges use record X X X X X X
Smokers’ preference X X X
Exploring the harm reduction/reversal potential (e.g.
reduction in biomarker known to be used as proxy for
risk prediction in CVD)

17. No changes in resting systolic BP (separately for each continuous phenotype)
Long effect of smoking abstinence/reduction
on BP and HR in smokers switching to ECs
Submitted for publication

18. 2013 ESH/ESC criteria for “high normal”
Modelling new strategies for harm reversal
n = 86 in ECLAT
n = 59 in ECLAT
Cut-off level

19. Long effect of smoking abstinence/reduction on BP and HR in smokers switching to ECs
SBP changes at Week 52 from baseline

20. Long effect of smoking abstinence/reduction on BP and HR in smokers switching to ECs
SBP changes at Week 52 from baseline
Harm
Reversal!

21. BLOOD PRESSURE CONTROL IN E-CIG USERS
K. Farsalinos et al. Int. J. Environ. Res. Public Health 2014
(N = 2162)
Dual users Single users

22. Learning Points
•Smoking abstinence by using ECs may lower elevated systolic BP
•Decreases were reported also in reducers
•ECs may be a helpful alternative to cigarettes in smokers with elevated BP

23. Flouris AD, et al.
Inhal Toxicol. 2013
baseline
3 min after
60 min after
Effects on user health:
spirometry

24. •RCTs in healthy smokers have shown that ECs are effective and safe
•No data about EC use among vulnerable populations, including people with asthma
•We investigated changes in subjective and objective asthma outcomes as well as safety in smoking asthmatics who switched to EC.

25. No significant differences between Pre-Baseline and Baseline Assessments
EC use in smoking asthmatics

26. 1st F/up
Visit
Assessment Timepoints
Pre- Baseline
Baseline
Forced Expiratory Volume in 1 second (L)
3.0
3.2
3.4
3.6
3.8
2nd F/up
Visit
**
FEV1
Improvement from baseline at 12 months
p=0.005
mean increase of 100mls
Harm
Reversal!
Regular EC use

27. Forced Vital Capacity (L)
3.8
4.0
4.2
4.4
4.6
4.8
1st F/up
Visit
Assessment Timepoints
Pre- Baseline
Baseline
2nd F/up
Visit
**
FVC
Improvement from baseline at 12 months
p=0.006
mean increase of 150mls
Harm
Reversal!
Regular EC use

28. FEF25-75 (L/sec)
2.4
2.6
2.8
3.0
3.2
3.4
1st F/up
Visit
Assessment Timepoints
Pre- Baseline
Baseline
2nd F/up
Visit
**
***
FEF25-75
Improvement from baseline at 6 and 12 months
p=0.006
mean increase of 250mls/sec
p=0.001
mean increase of 360mls/sec
Harm
Reversal!
Regular EC use

29. Pre-
Baseline
Methacholine PC20 (mg/mL)
1.0
1.5
2.0
2.5
3.0
3.5
Baseline 2nd F/up
Visit
1st F/up
Visit
Assessment Timepoints
**
Methacholine PC20
Improvement from baseline at 12 months
p=0.003
mean increase of 1.2 DD
Harm
Reversal!
Regular EC use

30. ACQ scores
1.2
1.4
1.6
1.8
2.0
2.2
2.4
1st F/up
Visit
Assessment Timepoints
Pre- Baseline
Baseline
2nd F/up
Visit
***
***
Juniper’s ACQ
Improvement from baseline at 6, 12 months
p=0.001
mean decrease of 0.43
p=0.001
mean decrease of 0.56
Harm
Reversal!
Regular EC use

31. Smoking habit and asthma exacerbations
Parameter
Baseline
1st follow-up visit
(6 months ± 1)
2nd follow-up visit
(12 months ± 2)
p value to
Baseline
p value to
Baseline
Cigarettes/day
21.9 (±4.5)
5.0 (±2.6)
<0.001
3.9 (±1.0)
<0.001
Exacerbations
1.17 (±0.9)
0.87 (±0.7)
0.296
0.78 (±0.7)
0.153
Frequent exacerbators (≥ 2 exacerbations; n=6)
halved their exacerbations at both follow-up visits

32. Safety and Tolerability
•No severe adverse reactions or acute exacerbations of asthma requiring hospitalisation/ITU admissions.
•ECs were well tolerated with dry mouth and throat irritation occasionally reported.

33. (N = 1173)
(N = 1062)
Dual users Single users
RESPIRATORY SYMPTOMS IN E-CIG USERS
K. Farsalinos et al. Int. J. Environ. Res. Public Health 2014

34. (N = 1173)
(N = 1062)
Dual users Single users
RESPIRATORY SYMPTOMS IN E-CIG USERS
K. Farsalinos et al. Int. J. Environ. Res. Public Health 2014

35. Learning Points
•EC use improves lung function, respiratory symptoms, subjective asthma outcomes
•Improvements were reported also in dual users
•Exposure to e-vapour in this vulnerable population did not trigger acute symtoms
•ECs are a safe alternative to cigarettes in smokers with chronic airways disease

36. Additional learning points from ECLAT
•Abuse potential was relatively low
•Improved sensorial quality (i.e. taste) is key to a wider adoption
•Efficiency (i.e. switching) can be maximized with better quality/technology (i.e. improved product reliability)

37. No. Of subjects
Reducers
0
50
100
150
200
250
300
Week-12
Week-52
Intention-to-treat
Quitters
Week-6
Week-24
Reduction and abstinence rates (%) throughout the study
22.3%
10.3%
10.7%
8.7%
26.9%
73.1%
Using e-cigs
Not using e-cigs
Abuse potential?
Caponnetto et al. Plos One 2013

38. Quitters
2wk
4wk
6wk
8wk
10wk
24wk
52wk
12wk
0
10
20
30
40
50
60
70
80
90
%
3%
NO nicotine
5.4 mg nicotine
7,2 mg nicotine
Inferior performance of group C compared to group A and B. Driven by what?

39. Week 6
Week 12
0
50
100
150
200
250
300
Cotinine (ng/ml)
Group A
Group B
Group C
Group A
Group B
Group C
Saliva cotinine levels in quitters among study groups
Group A: 24 mg/ml nicotine
Group B: 18 mg/ml nicotine
Group C: no nicotine
Is it nicotine? I do not think so!
Ordinary concentration threshold for regular smokers

40. Score
Q1
Q2
Q3
Group C
Group B
Group A
Week-24
Q1
Q2
Q3
Week-52
0
2
4
6
8
10
12
Q1
Q2
Q3
Week-12
”how much do you rate this EC compared to your own brand?”
Participants’ liking of the product
VAS score
VAS from 0 to 10 points (0 = being ‘completely unsatisfied’, 10 being = ‘fully satisfied’)

41. COMPLAINTS/CONCERNS
0
10
20
30
40
50
60
70
80
C: no nic
B: medium nic
A: high nic
CONS, W-12
No. times reported
poor taste
heavy
bulky
mulfunctions
p=0.002
…or is it taste? I do think so!

42. 0
10
20
30
40
50
60
70
80
C: no nic
B: medium nic
A: high nic
CONS, W-12
No. times reported
poor taste
discomfort
heavy
bulky
mulfunctions
p=0.002
p=0.02
COMPLAINTS/CONCERNS

43. Best results – an act of balance
Aroma
Nicotine levels
Liquidware
Hardware
Reliability
Convenience
User satisfaction/appeal

44. E-Cig: a product in (fast) evolution
ECLAT was planned in the 2009 when E-cig technology was in its infancy
The future
A.D. 2009
Future studies will have to focus on improved technology and
overall customer satisfaction
A.D. 2014
Improved product reliability Better taste More nicotine delivery

45. 0
10
20
30
40
50
60
70
50% reduction 80% reduction abstinence reduction+abstinence failure
cigalike
cigalike
cigalike
cigalike
cigalike
Success rates at 6 months: Cigalikes vs PVs
Combined data: Polosa, et al. BMC Public Health 2011 and Polosa, et al. BMC Public Health 2014

46. 0
10
20
30
40
50
60
70
50% reduction 80% reduction abstinence reduction+abstinence failure
cigalike
cigalike
cigalike
cigalike
cigalike
2° generation PVs
2° generation PVs
2° generation PVs
2° generation PVs
2° generation PVs
Combined data: Polosa, et al. BMC Public Health 2011 and Polosa, et al. BMC Public Health 2014
Success rates at 6 months: Cigalikes vs PVs

47. 0
10
20
30
40
50
60
70
50% reduction 80% reduction abstinence reduction+abstinence failure
cigalike
cigalike
cigalike
cigalike
cigalike
2° generation PVs
2° generation PVs
2° generation PVs
2° generation PVs
2° generation PVs
Combined data: Polosa, et al. BMC Public Health 2011 and Polosa, et al. BMC Public Health 2014
Success rates at 6 months: future gen models
Future generation model image

48. Acknowledgments