Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes

Introduction: Adherence to pharmacotherapies for tobacco dependence, such as varenicline, is necessary for effective treatment. The relationship between varenicline adherence, determined by commonly used indirect (i.e., self-reported pill counts) and infrequently used direct (i.e., varenicline levels) methods, and abstinence outcomes have not been previously examined, nor has their impact on the outcomes of a genetically randomized clinical trial been assessed. Methods: At Week 1 following target quit date, self-reported pill count and salivary varenicline levels were obtained from participants (N = 376) in a smoking cessation clinical trial (NCT01314001). Point-prevalence abstinence was biochemically-verified by salivary cotinine at Week 1 and by exhaled carbon monoxide at Week 1, end-of-treatment, 6 and 12 months following treatment. Blood nicotine metabolite ratio (NMR) was obtained at baseline. Results: Adherent individuals based on varenicline levels were significantly more likely to be abstinent than non-adherent individuals at Week 1 (odds ratios [ORs] 1.92–3.16, p's≤0.006), end-of-treatment (OR = 2.53, p =.004), and six months following treatment (OR = 2.30, p =.03). In contrast, pill counts did not consistently predict abstinence. Including direct measures of adherence enhanced the association between rate of nicotine metabolism (NMR) and end-of-treatment abstinence; normal metabolizers (NMR ≥ 0.31) were significantly more likely than slow metabolizers (NMR < 0.31) to be abstinent at end-of-treatment (OR = 2.00, p =.005). Conclusion: Adherence based on salivary varenicline, rather than on pill counts, is predictive of Week 1 abstinence, irrespective of the biomarker of abstinence assessed, and of long-term abstinence. Direct measures of adherence enhance the ability to assess the impact of a biomarker or genetic marker on abstinence outcomes.