Effect of Extending the Duration of Prequit Treatment With Varenicline on Smoking Abstinence: A Randomized Clinical Trial

• Published in: JAMA network open 2022-11, Vol.5 (11), p.e2241731
• Main Authors: Hawk, Jr, Larry W, Tiffany, Stephen T, Colder, Craig R, Ashare, Rebecca L, Wray, Jennifer M, Tyndale, Rachel F, Brandon, Thomas H, Mahoney, Martin C
• Format: Article
• Language: English
• Subjects: Abstinence; Animals; Benzazepines - therapeutic use; Clinical trials; Female; Nicotinic Agonists - therapeutic use; Online Only; Original Investigation; Quinoxalines - therapeutic use; Self report; Smoking; Smoking - drug therapy; Smoking - epidemiology; Smoking Cessation - methods; Substance Use and Addiction; Varenicline - therapeutic use
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2022.41731

Even with varenicline, the leading monotherapy for tobacco dependence, smoking abstinence rates remain low. Preliminary evidence suggests that extending the duration of varenicline treatment before quitting may increase abstinence. To test the hypotheses that, compared with standard run-in varenicline treatment (1 week before quitting), extended run-in varenicline treatment (4 weeks before quitting) reduces smoking exposure before the target quit date (TQD) and enhances abstinence, particularly among women. This double-blind, randomized, placebo-controlled clinical trial enrolled participants from October 2, 2017, to December 9, 2020, at a single-site research clinic in Buffalo, New York. Of 1385 people screened, 320 adults reporting smoking 5 or more cigarettes per day (CPD) were randomized and followed up for 28 weeks. Data were analyzed from August 2021 to June 2022. In the pre-TQD period (weeks 1-4), the extended run-in group received 4 weeks of varenicline; the standard run-in group received 3 weeks of placebo followed by 1 week of varenicline. Both groups received open-label varenicline during weeks 5 to 15 and brief quit counseling at 6 clinic visits. The primary outcome consisted of cotinine-verified (at end of treatment [EOT]) self-reported continuous abstinence from smoking (in CPD) during the last 4 weeks of treatment. Secondary outcomes included bioverified self-report of continuous abstinence at the 6-month follow-up and percentage of reduction in self-reported smoking rate during the prequit period (week 1 vs week 4). A total of 320 participants were randomized, including 179 women (55.9%) and 141 men (44.1%), with a mean (SD) age of 53.7 (10.1) years. Continuous abstinence during the final 4 weeks of treatment (weeks 12-15; EOT) was not greater in the extended run-in group (64 of 163 [39.3%]) compared with the standard run-in group (57 of 157 [36.3%]; odds ratio [OR], 1.13 [95% CI, 0.72-1.78]), nor was the hypothesized group × sex interaction significant (OR, 0.52 [95% CI, 0.21-1.28]). Similar nonsignificant results were obtained for continuous abstinence at the 6-month follow-up. The mean (SE) decrease in self-reported smoking rate during the prequit period was greater in the extended run-in group (-38.8% [2.8%]) compared with the standard run-in group (-17.5% [2.7%]). Among adult daily smokers, extending the duration of prequit varenicline treatment beyond the standard 1-week run-in period reduced prequit smoking exposure but, more importa