The plant-based alkaloid cytisinicline, when coupled with behavioural support, shows promise in the treatment of e-cigarette users who seek to break the habit.
In the 12-week, phase II ORCA-V1 trial, biochemically verified continuous e-cigarette abstinence during the last 4 weeks of treatment—the primary study endpoint—was recorded in 31.8 percent of participants who received cytisinicline. This number was twice as high as that seen among those who received placebo (15.1 percent). [JAMA Intern Med 2024; doi:10.1001/jamainternmed.2024.1313]
Treatment with cytisinicline was associated with a more than twofold greater odds of achieving the primary endpoint compared with placebo (odds ratio [OR], 2.64, 95 percent confidence interval [CI], 1.06–7.10; p=0.04). This benefit was consistent across subgroups defined by age, sex, race, history of cigarette smoking, e-cigarette dependence, age of vaping initiation, or e-liquid flavour used.
“Cytisinicline was well tolerated by participants, who reported no treatment-related serious adverse events and few troubling adverse effects, and adhered well to the treatment schedule,” the investigators said.
Treatment-emergent adverse events (TEAEs) occurred in 50.9 percent of participants in the cytisinicline group and in 54.7 percent in the placebo group, most of which were mild or moderate in severity. The most TEAEs with cytisinicline were abnormal dreams, insomnia, anxiety, headache, fatigue, and upper respiratory tract infection. Four participants on cytisinicline and three on placebo discontinued treatment due to TEAEs. There were no clinically meaningful changes seen in blood pressure, heart rate, laboratory values, or electrocardiogram results during treatment.
No increase in relapse risk
“Attempting to quit vaping could potentially lead some individuals, especially former cigarette smokers, to transition from e-cigarettes back to smoking cigarettes or to dual use of both products to sustain nicotine dependence. During the last 4 weeks of treatment, 7.5 percent of participants met criteria for possible cigarette smoking, with similar rates in cytisinicline and placebo groups,” the investigators noted.
Importantly, there was no evidence of a heightened risk of relapse to smoking or dual use among participants who received cytisinicline. This aligns with the drug’s demonstrated efficacy for smoking cessation and its hypothesized mechanism of action as a partial nicotine receptor agonist that prevents the reinforcement of smoking, as the investigators pointed out.
Meanwhile, results for the secondary endpoints of biochemically confirmed abstinence at other time points in the trial supported the finding of an overall benefit with cytisinicline versus placebo to aid vaping cessation but showed no significant between-group differences (weeks 3-6: 24.3 percent vs 15.1 percent, p=0.22; weeks 6-9: 30.8 percent vs 17 percent, p=0.09; weeks 9-16: 23.4 percent vs 13.2 percent, p=0.15).
ORCA-V1 included 160 adults (mean age 33.6 years, 51.9 percent female, 71.9 percent formerly smokers) who vaped nicotine daily, sought to quit, and did not currently smoke cigarettes. These participants were randomly assigned to treatment with either cytisinicline 3 mg (n=107) or placebo (n=53), taken three times daily for 12 weeks, in addition to weekly behavioural support. A total of 131 participants (81.9 percent) completed the trial.
“This study adds to the meagre evidence of pharmacotherapy for vaping cessation. To our knowledge, it is the first trial to test cytisinicline for this indication, and it did so using a new dosing regimen with demonstrated smoking cessation efficacy in a US population,” the investigators said.
“The promising findings warrant confirmation in a trial with a larger sample size and longer duration of posttreatment follow-up,” they added.