Cytisine produces submaximal dopaminergic stimulation to reduce craving and withdrawal while reducing the reinforcing effects of nicotine, supporting smoking cessation.Results from the Italian RISP* trial presented at WCLC 2026 show improvement in smoking cessation rates following treatment with cytisine, a partial agonist of α4β2nicotinic acetylcholine receptors.
“Cytisine produces submaximal dopaminergic stimulation to reduce craving and withdrawal while reducing the reinforcing effects of nicotine, supporting smoking cessation,” noted Dr Massimiliano Cani from Turin University in Italy.
Among cytisine users in the general population, smoking cessation rate was 50.1 percent. This was six times higher than that observed among those who only received counselling (8.1 percent). The adjusted odds ratio (aOR) was 14.53 (p<0.0001). The OR was adjusted for comorbidities, including pulmonary and anxiety/stress-related symptoms; pack-years; and baseline motivation to quit.
The cytisine group also had a significantly higher rate of tobacco reduction than the group who received counselling only (23.4 percent vs 10 percent; p<0.0001). [WCLC 2026. abstract OA07.05]
The most common adverse events (AEs) were nausea, insomnia, abdominal discomfort, and headache. There were no new safety signals identified.
Adults aged ≥65 years
The findings were similar among adults aged ≥65 years. Compared with those who received counselling only, the counselling plus cytisine group had a substantially higher tobacco cessation rate (49.1 percent vs 8.2 percent; aOR, 12.65; p<0.0001) and tobacco reduction rate (26.4 percent vs 12.5 percent; p<0.0001).
However, despite the efficacy of cytisine, current European guidelines generally do not recommend cytisine in this subgroup, Cani noted. “There is insufficient data supporting cytisine; there are concerns about potential side effects, interactions with comorbidities, and concomitant therapies; and there is no validated dose adjustment schedule for this population.”
The most common comorbidity among cytisine users was hypertension (46.3 percent), followed by chronic obstructive pulmonary disease (16.6 percent), anxiety/stress-related symptoms (13.3 percent), type 1/2 diabetes (13.1 percent), and cardiac arrhythmias (6.1 percent).
The AEs observed in this subgroup were comparable to those reported in the general population. Among those who discontinued treatment, 26.1 percent reported at least one AE, the most common being nausea, headache, and insomnia.
“All AEs were grade 1 according to CTCAE** v5.0. No new safety signals were identified, and no associations were observed between comorbidities, concomitant medications, and AEs,” said Cani.
The RISP programme
This programme has been active across 18 centres in Italy since October 2022. Funded by the Italian Ministry of Health, this prospective, randomized study aimed to assess the feasibility of a lung cancer screening programme with low-dose computed tomography (LDCT) within the Italian National Health Service.
Participants included current tobacco users (≥30 pack-years) or those who had quit for ≤15 years, who have not been diagnosed with cancer within 5 years. After LDCT at baseline, participants were randomized 1:1 to annual or biennial LDCT screening.
Current smokers at enrolment were invited to participate in a structured smoking cessation programme. Of the 3,548 volunteers, 2,173 underwent counselling alone (8.4 percent women), and 1,375 received counselling and cytisine (51.5 percent women). Among those aged ≥65 years (n=1,194; median age 68 years, 40 percent women), 766 received counselling only, and 428 received counselling and cytisine.
Counselling was done either individually or by group. Cytisine 1.5 mg tablets were provided following a 40-day dose escalation and de-escalation schedule.
Cani shared that in another study, longer cytisine regimens (84-day schedule) are associated with higher smoking cessation rates with a comparable safety profile and should thus be considered in future strategies.
Participants who resumed smoking and those who had not previously received cytisine are being offered cytisine retreatment. Follow-up assessments will be conducted at 1 year and 2 years to further evaluate potential relapses.