Increased risk of relapse after stopping nicotine replacement therapies: a mathematical modelling approach

To describe the effect of nicotine replacement therapy (NRT) on the risk of relapse as a function of time since the quit date.

Meta-analysis of 21 published, randomized, controlled clinical trials, comparing NRT to placebo.

A total of 6644 smokers were treated with NRT and 2766 smokers treated with placebo.

During treatment with the medication, NRT reduced the hazard ratio (HR) significantly compared with placebo [early HR = 0.62 (95% CI: 0.58-0.67)]. At the end of the average treatment duration (145 days), the HR was 0.81 (95% CI: 0.71-0.94), showing that the benefit was still present at this time. After stopping treatment, the HR increased progressively up to a value of 1.44 (95% CI, 1.18-1.76) showing that the risk of relapse was higher after stopping NRT than after stopping placebo. If NRT and placebo had not been stopped, the HR of smoking relapse would have been established at 0.95 (95% CI: 0.76-1.18, P = 0.64), indicating a similar risk of relapse with NRT and placebo. Moreover, the observed HR of smoking relapse was significantly higher than the expected HR of smoking relapse if NRT had been continued: the difference in HR is 1.51 (95% CI: 1.16-1.98, P < 0.003). This suggests that if NRT had been been continued, around 50% of relapses could have been prevented.

The protective effect of NRT against relapse slowly decreases as a function of time. After stopping NRT, the risk of relapse increases. It may be more beneficial not to stop NRT after the usual 3-6-month treatment period but to use NRT for longer periods of time.