Personalized Smoking Cessation: Interactions between Nicotine Dose, Dependence and Quit-Success Genotype Score

Abstract

Improving and targeting nicotine replacement therapy (NRT) are cost-effective strategies for reducing adverse health consequences for smokers. Treatment studies document the efficacy of pre-cessation NRT and support important roles for level of nicotine dependence and pre-cessation smoking reduction in successful quitting. However, prior work has not identified the optimal pre-cessation dose or means for personalizing NRT. Genome wide association has identified groups of genomic markers that are associated with successful quitting, allowing us to develop a v1.0 "quit success" genotype score. We now report influences of v1.0 quit success genotype score, level of dependence and pre-cessation smoking reduction in a smoking cessation trial that examined effects of 21 vs 42 mg/24 h pre-cessation NRT. 479 smokers were randomized to 21 or 42 mg NRT, initiated 2 weeks prior to target quit dates.We monitored self-reported abstinence and end-expired air carbon monoxide (CO). Genotyping used Affymetrix arrays. The primary outcome was 10-week continuous smoking abstinence. NRT dose, level of nicotine dependence and genotype scores displayed significant interactive effects on successful quitting. Successful abstinence was also predicted by CO reductions during pre-cessation NRT. These results document ways in which smoking cessation strategies can be personalized based on levels of nicotine dependence, genotype scores and CO monitoring. These assessments, taken together, can help to match most smokers with optimal NRT doses and to rapidly identify some who may be better treated using other methods. Molecular Medicine www.molmed.org UNCORRECTED PROOFCigarette smoking is a significant cause of premature death and disease 1 . Successfully quitting and maintaining abstinence reduce risks to smokers [2][3][4] . However, success rates following attempts to quit smoking remain modest. One year after unaided attempts to quit smoking, abstinence rates are less than 5% 5,6 . Even with pharmacologic aids that include nicotine replacement therapy (NRT), bupropion and varenicline, long-term abstinence rates are less than 25% 7, 8 .Pre-cessation NRT initiates nicotine patch treatment two weeks prior to a target quit date 9, 10 . The 21 mg/24 hour dose pre-cessation dose used to date is well tolerated by most smokers 9, 10 and consistently enhances quit rates: recent meta-analyses show a 1.8-2.2 fold greater likelihood of success than conventional NRT 11,12 . However, neither dose/response data nor clear-cut recommendations for personalizing pre-cessation NRT have been reported.More effective smoking cessation might result from personalizing existing treatments based on characteristics of individual smokers. Previous research has identified phenotypic and genotypic variables that might aid in predicting likelihood of success in smoking cessation and/or differential responses to different treatment regimens. In smoking cessation trials, smokers who score higher on the Fagerström Test for Nicotine Dependence (FTND), and thus display ...

Does cigarette reduction while using nicotine replacement therapy prior to a quit attempt predict abstinence following quit date?

“…We hypothesized that the association between reduction and quitting reported previously 1, 2, 3, 5 could have arisen, because people felt that they ought to reduce smoking intentionally while using cessation medication. We did not find strong evidence that the strength of association between reduction and cessation varied by trial arm.…”

“…For each participant we calculated the percentage change in baseline CPD and CO between visits 1 and 3. We also dichotomized these variables because reduction by at least 50% has been used previously as, or has been found to be, an indicator of response to medications in research studies 3, 5.…”

“…In four of these trials, participants used nicotine replacement therapy (NRT) for 2 weeks prior to quitting 1, 2, 3, 4. Participants who reduced consumption by more than the median (56%) while smoking and using NRT were found in one study to be more than three times more likely to stop smoking than people reducing less than the median 3.…”

“…In four of these trials, participants used nicotine replacement therapy (NRT) for 2 weeks prior to quitting 1, 2, 3, 4. Participants who reduced consumption by more than the median (56%) while smoking and using NRT were found in one study to be more than three times more likely to stop smoking than people reducing less than the median 3. Similarly, in people using varenicline for 4weeks prior to quit day, those who reduced consumption (indicated by cotinine concentration) by more than 50% were approximately three times more likely to achieve abstinence than those not reducing by this amount 5.…”

“…The second aim is to examine two plausible mechanisms that might explain this association. The explanation favoured by the investigators in the aforementioned studies 1, 2, 3, 5 is that smoking reduction is unwilled and occurs because medication met the need to smoke, and hence will support smokers adequately after they try to stop smoking. However, there is a second possible explanation.…”