Effect of Cytisine vs Varenicline on Smoking Cessation: A Randomized Clinical Trial

Effect of Cytisine vs Varenicline on Smoking Cessation: A Randomized Clinical Trial
Kristopher Nguyen, PharmD, New Ulm Medical Center

Background: Tobacco use remains a large modifiable risk factor that, when stopped, can impact patient health in a positive and significant way. Treatment choices include both over-the-counter and prescription medications with varenicline being an effective and popular, albeit costly, option. Cytisine is a plant-derivative that is a selective partial agonist at nicotinic acetylcholine receptors and has been used in European countries as a smoking cessation aid for decades. Cytisine has not been evaluated by the Food and Drug Administration (FDA) and is not available in the US; however, past trials have demonstrated safety and efficacy of cytisine as a treatment option.

Purpose: The objective of the study was to evaluate whether cytisine was non-inferior to varenicline as a smoking cessation medication. 

Study Design: A non-inferiority, open-label randomized clinical trial was completed in Australia from November 2017 through May 2019. Eligible patients were at least 18 years of age, a current daily smoker, and willing to make a quit attempt using medications. A total of 1,452 participants were randomized to receive either varenicline 0.5 mg titrated to 1 mg twice daily for an 84-day course of treatment or cytisine 1.5 mg six times daily for a 25-day course of therapy. The primary outcome was continuous abstinence from smoking which was determined by patient self-report of not having smoked five or more cigarettes during the 6-month period preceding the 7-month follow-up and verified by a carbon monoxide breath test. Follow-up was conducted at 2, 4, 16, and 28 weeks for both groups. The primary safety outcome was the difference in the rate of adverse events between groups. 

Results: For the primary endpoint, cytisine was inferior to varenicline for continuous abstinence from smoking with 6-month abstinence rates at 11.7% for cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI - 5.02 to ∞]; P=0.03) with -5.0% being the cut off for noninferiority. The incidence rate ratio (IRR) for self-reported adverse events occurred less frequently in the cytisine group (997) compared with the varenicline group (1,206) (IRR 0.88 [95% CI 0.81 - 0.95]; P=0.002). The most frequently reported adverse events were abnormal dreams and nausea which were less frequent in the cytisine group. Baseline characteristics, smoking history, and average cigarettes per day were balanced across both treatment groups.

Conclusions: Based on the results of this study, cytisine was inferior to varenicline as a therapeutic option for continuous abstinence rates from smoking. There were several limitations present such as the open-label design, unclear optimal dose and duration of cytisine treatment, and limited behavioral therapy offered to patients. Another limitation was that the carbon monoxide test used for the primary outcome can only detect smoking within 24 hours. A promising finding was the significantly lower rates of adverse events in the cytisine group.

Key Points: Cytisine has not been evaluated by the FDA and is not available as a treatment option in the US. Although this trial found cytisine to be inferior to varenicline in continuous smoking abstinence rates, cytisine still has potential as a safe and efficacious treatment option. Future blinded, randomized controlled trials need to be performed in order to further assess efficacy and safety. 

 

Reference:

  1. Courtney R, McRobbie H, Tutka P. Effect of cytisine vs varenicline on smoking cessation: a randomized clinical trial. JAMA. 2021;326(1):56-64. doi:10.1001/jama.2021.7621

 

Background: Tobacco use remains a large modifiable risk factor that, when stopped, can impact patient health in a positive and significant way. Treatment choices include both over-the-counter and prescription medications with varenicline being an effective and popular, albeit costly, option. Cytisine is a plant-derivative that is a selective partial agonist at nicotinic acetylcholine receptors and has been used in European countries as a smoking cessation aid for decades. Cytisine has not been evaluated by the Food and Drug Administration (FDA) and is not available in the US; however, past trials have demonstrated safety and efficacy of cytisine as a treatment option.

 

Purpose: The objective of the study was to evaluate whether cytisine was non-inferior to varenicline as a smoking cessation medication. 

 

Study Design: A non-inferiority, open-label randomized clinical trial was completed in Australia from November 2017 through May 2019. Eligible patients were at least 18 years of age, a current daily smoker, and willing to make a quit attempt using medications. A total of 1,452 participants were randomized to receive either varenicline 0.5 mg titrated to 1 mg twice daily for an 84-day course of treatment or cytisine 1.5 mg six times daily for a 25-day course of therapy. The primary outcome was continuous abstinence from smoking which was determined by patient self-report of not having smoked five or more cigarettes during the 6-month period preceding the 7-month follow-up and verified by a carbon monoxide breath test. Follow-up was conducted at 2, 4, 16, and 28 weeks for both groups. The primary safety outcome was the difference in the rate of adverse events between groups. 

 

Results: For the primary endpoint, cytisine was inferior to varenicline for continuous abstinence from smoking with 6-month abstinence rates at 11.7% for cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI - 5.02 to ∞]; P=0.03) with -5.0% being the cut off for noninferiority. The incidence rate ratio (IRR) for self-reported adverse events occurred less frequently in the cytisine group (997) compared with the varenicline group (1,206) (IRR 0.88 [95% CI 0.81 - 0.95]; P=0.002). The most frequently reported adverse events were abnormal dreams and nausea which were less frequent in the cytisine group. Baseline characteristics, smoking history, and average cigarettes per day were balanced across both treatment groups.

 

Conclusions: Based on the results of this study, cytisine was inferior to varenicline as a therapeutic option for continuous abstinence rates from smoking. There were several limitations present such as the open-label design, unclear optimal dose and duration of cytisine treatment, and limited behavioral therapy offered to patients. Another limitation was that the carbon monoxide test used for the primary outcome can only detect smoking within 24 hours. A promising finding was the significantly lower rates of adverse events in the cytisine group.

 

Key Points: Cytisine has not been evaluated by the FDA and is not available as a treatment option in the US. Although this trial found cytisine to be inferior to varenicline in continuous smoking abstinence rates, cytisine still has potential as a safe and efficacious treatment option. Future blinded, randomized controlled trials need to be performed in order to further assess efficacy and safety. 

 

Teaser Summary

Cytisine is a plant-derivative product that has been used in European countries as a smoking cessation aid for decades. Will a randomized, open-label study show that cytisine is non-inferior to varenicline, a proven efficacious medication, for continuous smoking abstinence?

 

Reference:

  1. Courtney R, McRobbie H, Tutka P. Effect of cytisine vs varenicline on smoking cessation: a randomized clinical trial. JAMA. 2021;326(1):56-64. doi:10.1001/jama.2021.7621