Real-world smoking cessation pharmacotherapy response stratified by nicotine metabolite ratio in Chinese smokers: findings from the China National Tobacco Cessation Cohort study (CNTCCS)

Nicotine metabolite ratio (NMR) might be a potential biomarker for smoking cessation pharmacotherapy. However, evidence on appropriate thresholds in Chinese smokers is limited. This study aimed to evaluate candidate NMR thresholds and real-world pharmacotherapy response according to NMR status in Chinese smokers. This real-world cohort study included 1,917 smokers from the China National Tobacco Cessation Cohort who initiated varenicline, bupropion, or nicotine gum. NMR was calculated as the ratio of trans-3′-hydroxycotinine to cotinine and analyzed continuously and dichotomized at the cohort median (0.24). The primary outcome was biochemically validated 7-day point smoking cessation abstinence rate at 24 weeks. Univariable and multivariable logistic regression models were used to assess the association between NMR and smoking cessation outcomes. Participants with lower NMR had higher 24-week abstinence rates than those with higher NMR (41.5% vs. 36.3%; adjusted OR = 1.32, 95% CI: 1.09–1.60, P = 0.005). Significant interactions were observed between NMR status and different pharmacotherapies (p for interaction <0.001). Among participants with higher NMR, varenicline achieved higher 24-week abstinence rates than bupropion (49.7% vs. 31.5%; adjusted OR = 2.10, 95% CI: 1.53–2.88, P < 0.001) and nicotine gum (49.7% vs. 22.8%; adjusted OR = 2.97, 95% CI: 1.96–4.50, P < 0.001), whereas among participants with lower NMR, abstinence rates were comparable across three pharmacotherapies. Findings were consistent in sensitivity analyses using alternative NMR thresholds of 0.27 and 0.31. In Chinese smokers, a cohort-derived NMR threshold of 0.24 identified differential pharmacotherapy response patterns. Varenicline was associated with higher abstinence rates among participants with higher NMR, supporting further evaluation of NMR as a potential biomarker for individualized smoking cessation treatment.