Increased doses of smoking cessation therapy improved quit rates following treatment failure
Raising doses of varenicline or nicotine replacement therapy increased abstinence rates in patients for whom an initial dose of varenicline or combined nicotine replacement therapy was ineffective, a two-part trial found.
For patients who did not achieve smoking abstinence after an initial quit attempt, increasing dosages of therapy helped, according to new results of a randomized clinical trial.
Researchers randomized 490 volunteers (43% women, 58% non-Hispanic White; mean age, 48.1 years) to receive six weeks of varenicline or combined nicotine replacement therapy (CNRT). After the initial six weeks, patients who were still smoking were rerandomized to continue therapy, switch, or increase medication dosage for an additional six weeks. The study took place between June 2015 and October 2019 at a Texas tobacco treatment clinic. Participants received an initial treatment of 2 mg of varenicline daily or CNRT of a 21-mg patch plus a 2-mg lozenge. In the second round, patients received either 3 mg or more of varenicline or a 42-mg patch plus lozenges. All participants smoked an average of 20 cigarettes per day upon randomization and received brief counseling on a weekly basis during the trial. Findings were published by JAMA on May 2.
After the first phase of the trial, 54 participants in the CNRT group were abstinent and continued their therapy. Forty participants who did not return for rerandomization were assigned to continue CNRT during phase 2 of the trial. Among the 191 nonabstainers, 151 were rerandomized, and end-of-treatment abstinence rates were 8% (95% credible interval [CrI], 6% to 10%) for the 90 participants who continued at the same dose, 14% (95% CrI, 10% to 18%) for the 50 participants who increased their dosage, and 14% (95% CrI, 10% to 18%) for the 51 participants who switched to varenicline (absolute risk difference, 6%; 95% CrI, 6% to 11%). The posterior probability that either strategy conferred benefit over continuing the initial dosage was greater than 99%.
At the end of the initial six weeks, 88 patients in the varenicline group were abstinent and continued their therapy. Among the 157 nonabstainers, 122 were rerandomized and 35 who didn't return for rerandomization were assigned to continue with their varenicline dose. Of the 39 patients who increased their dose, the end-of-treatment abstinence rate was 20% (95% CrI, 16% to 26%). None of the 41 participants who switched to CNRT quit, compared to 3% (95% CrI, 1% to 4%) in the 77 who continued their varenicline (absolute RD, −3%; 95% CrI, −4% to −1%). The posterior probability that continuing varenicline at the initial dosage was worse than switching to a higher dosage was greater than 99%. Increasing doses of varenicline had an absolute risk difference of 18% (95% CrI, 13% to 24%).
An assessment of secondary outcomes at six months showed that only increased doses of CNRT and varenicline provided benefit over continuation of the initial treatment dosages, the authors wrote. There was no evidence of increased risk of adverse events when patients increased their medication doses.
One limitation to the study is that researchers used 2-mg instead of 4-mg lozenges, which may have limited the efficacy of the CNRT approach for some people who smoke more heavily. In addition, increasing the number of 21-mg patches to two or increasing varenicline to 3 mg is considered off-label prescribing, the researchers cautioned. Overall, the results "provide clinicians with guidance on the best rescue strategies for nonabstinence following an initial quit attempt," they concluded.