Investigational Drug Could Help Vapers Quit

Adding daily use of the investigational drug cytisinicline to behavioral support doubled abstinence rates in e-cigarette users attempting to quit, a randomized phase II trial showed.

In the 12-week study, 31.8% of the vapers assigned to take the plant-based alkaloid achieved biochemically confirmed continuous e-cigarette abstinence over the final 4 weeks of treatment, as compared with 15.1% of those assigned to placebo (OR 2.64, 95% CI 1.06-7.10, P=0.04), reported researchers led by Nancy Rigotti, MD, of Harvard Medical School in Boston.

The study, which included 160 adults who used nicotine e-cigarettes but not traditional cigarettes, found a consistent effect across subgroups, according to the findings in JAMA Internal Medicine.

"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," wrote Rigotti and coauthors.

Vaping in the U.S. is on the rise, particularly among young adults. Though a majority of users report interest in eventually quitting, many need help in doing so, the researchers explained.

Few trials have evaluated tools for quitting vaping specifically: a pilot study indicated efficacy with nicotine replacement and one randomized trial showed that varenicline (Chantix) -- approved as a quit aid for traditional cigarettes -- improved abstinence rates among e-cigarette users.

"No medication has been approved by the FDA for vaping cessation," Rigotti said in a press release. "Our study indicates that cytisinicline might be an option to fill this gap and help adult vapers to stop using e-cigarettes."

Cytisinicline is a partial agonist of α4β2 nicotinic acetylcholine receptors that mediate nicotine dependence. In a prior randomized trial, the drug proved effective in helping traditional cigarette smokers quit.

"The results of our study need to be confirmed in a larger trial with longer follow-up," said Rigotti, "but they are promising." To that end, drugmaker Achieve Life Sciences said it is meeting with the FDA to discuss plans for a phase III trial of cytisinicline as a cessation aid for e-cigarette users.

While the current study excluded dual users (people who vape and smoke traditional cigarettes), the researchers noted that cytisinicline did not appear to increase the risk of relapse to smoking or dual use. During the end-of-treatment period, 6.5% of cytisinicline users met criteria for possible cigarette smoking versus 9.5% of placebo recipients.

While e-cigarettes can help people quit smoking, and are generally considered safer than combustible cigarettes, they are not without potential harm.

"In the national and worldwide discourse about the public health benefits vs harm of e-cigarettes there has been minimal focus on how to support individuals who want to stop using e-cigarettes, leading to a critical lack of evidence-based treatments," said Suchitra Krishnan-Sarin, PhD, and Lisa M. Fucito, PhD, both of the Yale School of Medicine in New Haven, Connecticut, in an editorial accompanying the study.

While some research attempts to help vapers quit have been modeled after those for traditional cigarettes, Krishnan-Sarin and Fucito noted that e-cigarettes have many unique characteristics that can enhance their appeal and potential for addiction (flavors, the ability to be discreetly used, higher nicotine concentrations).

As such, helping vapers quit may require different approaches, the editorialists said.

"Even individuals who start using e-cigarettes after quitting cigarette smoking report that they feel more addicted and believe that they are consuming more nicotine," wrote Krishnan-Sarin and Fucito. "The efficacy of medications like cytisinicline for people with greater addiction from the use of these novel e-cigarettes may be diminished."

The current study, ORCA-V1 (Ongoing Research of Cytisinicline for Addiction), included 160 vapers looking to quit who were enrolled at five U.S. sites. The individuals were randomized 2:1 to either 12 weeks of cytisinicline (3 mg, three times per day) or matching placebo on top of 13 planned behavioral support sessions.

Participants were eligible if they used e-cigarettes with nicotine daily, had a positive saliva cotinine test result (≥30 ng/mL), and were willing to set a quit date between 7-14 days following the start of taking the study drug. Dual users and people who recently used a smoking cessation drug were excluded, as were those with certain medical conditions.

Average participant age was about 34 years, and 52% were women. Most were white (84.4%), while 8.8% were Black, 5.6% were of Hispanic ethnicity, and 3.8% were Asian. More than three-fourths were prior cigarette smokers.

The primary outcome of the study was continuous e-cigarette abstinence during the final 4 weeks of treatment (weeks 9-12), biochemically confirmed via saliva samples tested for the nicotine metabolite cotinine. Cytisinicline's effect appeared consistent across "subgroups defined by age, sex, race, history of cigarette smoking, e-cigarette dependence, age of vaping initiation, or e-liquid flavor used," according to the researchers.

Secondary outcomes included biochemically confirmed abstinence at other time points in the trial, but showed no statistically significant differences between groups, though they tended to favor the intervention:

• Weeks 3-6 (24.3% vs 15.1%, P=0.22)
• Weeks 6-9 (30.8% vs 17%, P=0.09)
• Weeks 9-16 (23.4% vs 13.2%, P=0.15)

Adverse events (AEs) were reported in 51% of the individuals in the cytisinicline arm and 55% of those in the placebo arm, with 28.3% and 18.9% considered related to treatment. No AEs in either group were serious, and fewer individuals on cytisinicline discontinued due to AEs (3.8% vs 5.7% with placebo). The most common AEs with cytisinicline, and which occurred more frequently than with placebo, included abnormal dreams (12.3%), insomnia (10.4%), and anxiety (9.4%).

Limitations included the small sample size, the largely white population and exclusion criteria, and the limited follow-up time, said Rigotti and colleagues.

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