The opinions expressed by the authors are their own, and this material should not be interpreted as representing the official viewpoint of the U.S. Department of Health and Human Services, the National Institutes of Health or the National Cancer Institute. Nicole Senft Everson served as a lead role for conceptualization, formal analysis, writing-original draft, and writing-review & editing. William M. P. Klein contributed equally for writing-review & editing and served in a supporting role for conceptualization. Scott S. Lee contributed equally for methodology and served in a supporting role for writing-review & editing. Rebecca Selove and Maureen Sanderson contributed equally for funding acquisition and served in a supporting role for writing-review & editing. William J. Blot contributed equally for resources and served in a supporting role for supervision and writing-review & editing. Rachel F. Tyndale contributed equally for resources and served in a supporting role for and writing-review & editing. Stephen King contributed equally for project administration and served in a supporting role for writing-original draft and writing-review & editing. Karen Gilliam contributed equally for project administration and served in a supporting role for writing-review & editing. Suman Kundu served as a lead role for formal analysis and served in a supporting role for writing-original draft and writing-review & editing. Mark Steinwandel served in a supporting role for data curation and writing-review & editing. Sarah J. Sternlieb served in a supporting role for project administration and writing-review & editing.

Introduction The nicotine metabolite ratio (NMR), a biomarker of CYP2A6-mediated nicotine metabolism, predicts efficacy of nicotine replacement therapy (NRT), with fast metabolizers benefiting less than slow metabolizers. Whether treatment support to optimize NRT use (henceforth “treatment support”) modifies this pharmacogenetic relationship is unknown. Methods Hospitalized adult daily smokers were assigned to one of two post-discharge smoking cessation interventions offering NRT and counseling: (1) Transitional Tobacco Care Management, which delivered enhanced treatment support via free combination NRT at discharge and automated counseling, and (2) a quitline-based approach representing usual care (UC). The primary outcome was biochemically verified 7-day point prevalence abstinence 6 months after discharge. Secondary outcomes were use of NRT and counseling during the 3-month intervention period. Logistic regression models tested for interactions between NMR and intervention, controlling for sex, race, alcohol use, and BMI. Results Participants (N=321) were classified as slow (n=80) or fast (n=241) metabolizers relative to the first quartile of NMR (0.012-0.219 vs. 0.221-3.45, respectively). Under UC, fast (vs. slow) metabolizers had lower odds of abstinence at 6 months (aOR 0.35, 95% CI 0.13-0.95) and similar odds of NRT and counseling use. Compared to UC, enhanced treatment support increased abstinence (aOR 2.13, 95% CI 0.98-4.64) and use of combination NRT (aOR 4.62, 95% CI 2.57-8.31) in fast metabolizers, while reducing abstinence in slow metabolizers (aOR 0.21, 95% CI 0.05-0.87; NMR-by-intervention interaction p=0.004). Conclusions Treatment support increased abstinence and optimal use of NRT among fast nicotine metabolizers, thereby mitigating the gap in abstinence between fast and slow metabolizers. Implications In this secondary analysis of two smoking cessation interventions for recently hospitalized smokers, fast nicotine metabolizers quit at lower rates than slow metabolizers, but providing fast metabolizers with enhanced treatment support doubled quit rates in this group and mitigated the disparity in abstinence between fast and slow metabolizers. If validated, these findings could lead to personalized approaches to smoking cessation treatment that improve outcomes by targeting treatment support to those who need it most.

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