1. Increasing Cessation Rates with NRT Gay Sutherland Research & Consultant Clinical Psychologist Tobacco Research Unit, Institute of Psychiatry, Kings College London & Specialist Smoking Cessation Clinic South London & Maudsley NHS Foundation Trust ENQ Conference 29 th – 30 th Jan 2009 (Paris)

2. NRT Re-Cap: n Doubles quit rates of both brief and intensive interventions n Reduces severity of withdrawal symptoms n Delays weight gain n Reduces relapse n Gives ~50% nicotine replacement n Very safe (if used by smokers!)

3. Efficacy (Odds Ratios) of NRT Cochrane 2008 Gum1.7 Patch1.7 Inhaler2.1 Nasal Spray2.5 Microtab/Lozenge2.1

4. Consistency of NRT Efficacy (Cochrane 2008) 4111 RCTs 422,732 smokers 4106 of 111 showed positive results

5. NRT Re-Cap: n Reduces severity of withdrawal symptoms and craving to smoke

6. Dose of NRT needs to be in this range

7. NRT Re-Cap: n Doubles quit rates of both brief and intensive interventions n Reduces severity of withdrawal n Delays weight gain n Reduces relapse n Gives ~50% nicotine replacement n Very safe (if used by smokers!)

8. But nothing like a cigarette!

10. Common False Beliefs About NRT Cummings (2004)

11. Common False Beliefs About NRT We Need to Address Cummings (2004) What % think NRT does not increase quit rates? 41%

12. Common False Beliefs About NRT We Need to Address Cummings (2004) What % think risk of addiction with the patch is as high or higher than for cigarettes? 54%

13. Common False Beliefs About NRT We Need to Address Cummings (2004) What % think risk of heart attacks from the patch is as high or higher than for cigarettes? 65%

14. Common False Beliefs About NRT We Need to Address Cummings (2004) What % think nicotine causes cancer? 67%

15. Public Perception of NRT n US national survey, 3,203 current and former smokers n 66% agreed that NRT is just as harmful as cigarettes or were unsure if true n Less likely to use NRT and if used, used less and for shorter time n Public education needed – how to do it? Shiffman et al. 2008, Addiction 103, 1371-1378

16. NRT efficacy is harmed by: Unrealistic expectations (magic cure, waiting for the drug to make me stop smoking) Unrealistic expectations (magic cure, waiting for the drug to make me stop smoking) Insufficient and incorrect use (fear of nicotine, using only when desperate) Insufficient and incorrect use (fear of nicotine, using only when desperate) Lack of preparation for the fact that oral products in particular may take time to get used to Lack of preparation for the fact that oral products in particular may take time to get used to

17. John Stapleton (2008) n n Since NRT was introduced 30 years ago its full potential has remained underdeveloped and under-researched n n Licence say: Start using NRT on day smoking stops; Use a limited dosage while not smoking Stop using NRT if smoking resumes Use for only 10–16 weeks, regardless of progress! Addiction (2008)

18. One Size Does Not Fit All!

19. Can we do better with NRT?

20. Better Ways of Using NRT Pre-Treatment before Quit Day? Pre-Treatment before Quit Day? Combination NRT? Combination NRT? Use Higher Doses? Use Higher Doses? Use During a Lapse or Slip? Use During a Lapse or Slip? Adapted from Hughes (2008) UKNSCC

21. Possible Rationale? Improve efficacy by separating nicotine levels from smoking and thus extinguishing smoking reinforcement Improve efficacy by separating nicotine levels from smoking and thus extinguishing smoking reinforcement Help smokers cut-down and increase their confidence in quitting Help smokers cut-down and increase their confidence in quitting Might get smokers used to NRT Might get smokers used to NRT

22. NRT Use Prior to Quitting Meta-analysis of 4 studies Meta-analysis of 4 studies Pre-treatment with patches for 2 weeks (3 studies) or 4 weeks (1 study) Pre-treatment with patches for 2 weeks (3 studies) or 4 weeks (1 study) 6-months abstinence OR=2.2 6-months abstinence OR=2.2 But: But: 3 studies by the same author 3 studies by the same author 4-week pre-treatment was the only study with negative results 4-week pre-treatment was the only study with negative results Shiffman and Ferguson (2008) Addiction, 103,

23. Better Ways of Using NRT n Pre-Treatment before Quit Day? n Combination NRT? n Use Higher Doses? n Use During a Lapse or Slip? Adapted from Hughes (2008) UKNSCC

24. Rationale for Combination NRT? Patch gives steady levels of nicotine easily plus oral top-ups when needed Patch gives steady levels of nicotine easily plus oral top-ups when needed Likely to lead to higher nicotine replacement levels Likely to lead to higher nicotine replacement levels

25. 35 30 25 20 15 10 5 0 Cues or Triggers to Smoke Tea/Coffee Concentration Reward Driving (Time) Habit Daily Event After a meal Social (peer pressure) Telephone Stress Boredom Alcohol

26. Central Role of Craving nBackground craving: n Steady during the day n Internal - needs no environmental triggers n Gradually reduces in intensity over a few weeks nEpisodic craving: n Occasional intense bursts n Triggered by environmental cues or mood n Decreases in frequency but NOT intensity for months n Caused by being in situations ex-smoker has not yet got habituated to Patch Faster Self-Dosed NRT

27. n Usually patch + faster self- administered product n 7 trials included in Cochrane review show overall benefit (OR=1.42) Combining 2 Different NRTs Silagy et al. (Cochrane Library)

28. What time of day do people relapse? (%) Brandon et al 1986

29. NICE Endorses Combination Therapy Consider offering a combination of nicotine patches and another form of NRT… to people who show a high level of dependence on nicotine or who have found single forms of NRT inadequate in the past. This meeting is sponsored GlaxoSmithKline Consumer Healthcare [NCQ/CW/0608/005] Feb 2008

30. …Craving predicts who is most likely to relapse….

32. Essential to get good craving relief early on in the quit attempt

33. Quitting early matters! Cease Trial: 25% of smokers abstinent in their 1 st week stayed quit for 1 yr vs only 2.7% of those who smoked in 1 st week Cease Trial: 25% of smokers abstinent in their 1 st week stayed quit for 1 yr vs only 2.7% of those who smoked in 1 st week A Patch study of 1,686 smokers also found early quitting the strongest predictor of sustained abstinence Of the 1st week quitters, 25% of those on NRT and 28% on placebo became long-term quitters vs only 4% (NRT) and 2% (placebo) if they smoked in the 1 st week Another study of 1,200 smokers found all but 1 of the 96 subjects who quit long-term, had quit during their 1st week

34. Better Ways of Using NRT Use it for Longer? Use it for Longer? Pre-Treatment before Quit Day? Pre-Treatment before Quit Day? Use Higher Doses? Use Higher Doses? Use During a Lapse or Slip? Use During a Lapse or Slip? Adapted from Hughes (2008) UKNSCC

35. European Respiratory Journal (1999) Higher Doses of NRT for Greater % Nicotine Replacement?

36. European Multi-Centre CEASE Trial RCT to see if higher dose and longer duration of use of 16hr daytime-only patches increase quit rates RCT to see if higher dose and longer duration of use of 16hr daytime-only patches increase quit rates 36 chest clinics in 17 countries 36 chest clinics in 17 countries 3,575 smokers took part (>14 cigs per day) 3,575 smokers took part (>14 cigs per day) Smokers randomized to 1 of 5 groups: Smokers randomized to 1 of 5 groups: n n 25mg patch (15 + 10mg) for 22 wks - 15mg for 2 wks - 10mg for 2 wks n n 25mg patch (15 + 10mg) for 8 wks - 15mg for 2 wks - 10mg for 2 wks -14 wks of placebo patches n n 15mg patch + placebo for 22 wks - 10mg for 4 wks n n 15mg patch + placebo for 8 wks - 10mg for 4 wks - 14 wks of placebo patches n n 2 x placebo patches for 26 wks Smokers also received behavioural support Smokers also received behavioural support

37. High dose Standard dose Placebo

38. CEASE Trial Results 1 yr sustained quit rates were: 1 yr sustained quit rates were: n High dose long duration = 15.4% n High dose standard duration = 15.9% n Standard dose long duration = 13.7% n Standard dose standard duration = 11.7% n Placebo = 9.9% n No sign. difference in quit rates between long and standard duration patch use High dose patches increased long-term quit rates High dose patches increased long-term quit rates But no advantage in using for longer than 8-12 weeks But no advantage in using for longer than 8-12 weeks

39. Higher nicotine doses also gave better relief of tobacco withdrawal symptoms

41. CEASE Trial - Safety Higher doses were well tolerated Higher doses were well tolerated Side-effects were mild and typical of NRT (eg skin irritation) Side-effects were mild and typical of NRT (eg skin irritation) No unexpected or serious adverse events No unexpected or serious adverse events

42. Higher Doses or Tailoring NRT (Cochrane 2008) Higher Doses of Patch: Higher Doses of Patch: 7 trials = 1.2 (OR) Tailoring Dose to Blood Levels: Tailoring Dose to Blood Levels: 2 small trials both report improvement

43. The Implications? A 25mg/16 hr patch will soon be launched in some European countries A 25mg/16 hr patch will soon be launched in some European countries Many clinicians are too cautious about dosing Many clinicians are too cautious about dosing SPCs for NRT usually have cut-offs based on cigs/day which are unduly conservative and not supported by the evidence SPCs for NRT usually have cut-offs based on cigs/day which are unduly conservative and not supported by the evidence

44. Better Ways of Using NRT Use it for Longer? Use it for Longer? Pre-Treatment before Quit Day? Pre-Treatment before Quit Day? Use Higher Doses? Use Higher Doses? Use During a Lapse or Slip? Use During a Lapse or Slip? Adapted from Hughes (2008) UKNSCC

45. Importance of Continuing NRT During a Lapse or Slip (Shiffman 2006) Prevention of a lapse or slip to full relapse = 7.1

46. Lapse Recommendations n Keep using NRT! n Increase Dose of Patch n Increase Dose of Acute NRT n Add a 2 nd NRT John Hughes 2008

47. Bottom Line n Max effort early on. Get good NRT dosing from the beginning n Be flexible - switch NRTs if smoker prefers n Use combinations n Use higher doses n Continue with NRT during lapses n Most important - keep re-treating failures!!!

48. John Hughes (2008 UKNSCC) Using NRT via guidelines is suboptimal treatment and should be discouraged Using NRT via guidelines is suboptimal treatment and should be discouraged Allowing fear of complaints or lawsuits to prevent optimal care is unethical Allowing fear of complaints or lawsuits to prevent optimal care is unethical