Prolonging varenicline prequit therapy period may not increase rates of continuing abstinence: JAMA

U.S.A.: Prequit varenicline treatment that lasted longer than the typical 1-week run-in time among adult daily smokers lowered prequit smoking exposure but, more crucially, did not significantly increase rates of continuing abstinence, according to a study published in JAMA Network Open.

Varenicline has been the most successful monotherapy for quitting smoking since 2006. Varenicline does not, however, have high rates of long-term abstinence.

However, these studies do not address the issue of whether longer run-in varenicline treatment is superior to normal varenicline treatment, according to Larry W. Hawk Jr., PhD, Department of Psychology, University at Buffalo and colleagues.

"Previous large RCTs have indicated that both standard and extended run-in varenicline therapies promote smoking cessation relative to placebo treatment," they wrote.

The investigators sought to assess the hypotheses that extended run-in varenicline treatment (4 weeks before quitting) improves abstinence, especially in women, and reduces smoking exposure before the target quit date (TQD), compared to regular run-in varenicline treatment (1 week before quitting).

From October 2, 2017, through December 9, 2020, volunteers were enrolled into this double-blind, randomized, placebo-controlled clinical experiment at a single-site research clinic in Buffalo, New York. 320 adults who reported smoking 5 or more cigarettes per day (CPD) out of 1385 participants who were tested were randomly assigned and followed up with for 28 weeks. Between August 2021 and June 2022, data were examined. The extended run-in group received 4 weeks of varenicline during the pre-TQD period (weeks 1-4), while the regular run-in group received 3 weeks of placebo and then 1 week of varenicline.

During weeks 5 to 15, both groups got open-label varenicline, along with brief quit-coaching sessions at six clinic visits. The main result was continuous self-reported abstinence from smoking (in CPD) over the final four weeks of treatment, as cotinine-verified (at end of treatment [EOT]). Secondary endpoints included the percentage of decrease in self-reported smoking rate during the prequit period and bioverified self-report of continued abstinence at the 6-month follow-up (week 1 vs week 4).

Key findings of the study:

• The odds ratio [OR], 1.13 [95% CI, 0.72-1.78] for continuous abstinence during the final four weeks of treatment (weeks 12–15; EOT) was not higher in the extended run-in group (64 of 163 [39.3%]) than in the standard run-in group (57 of 157 [36.3%]), and the predicted group–sex interaction was not significant (OR, 0.52 [95% CI, 0.21–1.28).
• At the 6-month follow-up, same non-significant findings were achieved for sustained abstinence.
• The extended run-in group experienced a larger mean (SE) decline in self-reported smoking rate during the prequit period compared to the normal run-in group (38.8% [2.8%] vs. 17.5% [2.7%]).

The authors came to the conclusion that participants would have many prequit opportunities to experience a decrease in reinforcement while smoking with a longer pre-TQD varenicline treatment. This would reduce prequit smoking exposure (without increasing craving or withdrawal) and improve postquit abstinence rates.

Testing these theories within the framework of a bigger, women-only multisite trial may be worth the effort, given that women typically struggle more with long-term abstinence than males, they continued.

REFERENCE

Hawk LW, Tiffany ST, Colder CR, et al. Effect of Extending the Duration of Prequit Treatment With Varenicline on Smoking Abstinence: A Randomized Clinical Trial. JAMA Netw Open. 2022;5(11):e2241731. doi:10.1001/jamanetworkopen.2022.41731