Efficacy of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for smoking cessation: a randomized placebo-controlled trial.

BACKGROUND AND AIMS: Nicotine vaccination has been proposed as a possible treatment to aid smoking cessation. First efficacy results of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo. The present study examined the efficacy of adding NicVAX versus placebo to varenicline and behavioural support as an aid in smoking cessation and relapse prevention. DESIGN: Randomized placebo-controlled trial. SETTING: Two research centres (Maastricht University Medical Centre and Slotervaart Hospital) in the Netherlands. PARTICIPANTS: A total of 558 smokers were assigned randomly to six injections with NicVAX (n = 278) or placebo (n = 280) both co-administered with open label varenicline and behavioural support. MEASURES: Outcomes were prolonged carbon monoxide-validated abstinence from weeks 9 to 52 (primary) and weeks 37 to 52 (secondary). We also performed a pre-planned subgroup analysis in the top 30% antibody responders. FINDINGS: There was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.62-1.29] or weeks 37 to 52 (33.8 versus 33.2%, OR = 1.03, 95% CI = 0.73-1.46). The top 30% antibody responders, compared to the placebo group, showed a non-significant tendency towards higher abstinence rates from weeks 37 to 52 (42.2 versus 33.2%, OR = 1.47, 95% CI = 0.89-2.42). CONCLUSION: The nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.

The efficacy and safety of a nicotine conjugate vaccine (NicVAX®) or placebo co-administered with varenicline (Champix®) for smoking cessation: study protocol of a phase IIb, double blind, randomized, placebo controlled trial.

BACKGROUND: A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood-brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX® co-administered with varenicline (Champix®) and intensive counseling as an aid in smoking cessation and relapse prevention. METHODS/DESIGN: Two centers will include a total of 600 smokers who are motivated to quit smoking. At week -2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7 days of varenicline treatment at week 1. Smokers will be followed up for 54 weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. DISCUSSION: This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline) to quit smoking. Although NicVAX® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain abstinence and prevent relapse. The results of this trial will give a unique insight in the potential of nicotine vaccination for relapse prevention. TRIAL REGISTRATION: ClinicalTrials.gov: (NCT00995033).

Evaluation of smoking cessation drug use and outcomes in the Netherlands.

OBJECTIVE: Several pharmacological therapies are available to help smokers quit. The aim was to investigate the utilisation and effectiveness of smoking cessation drugs in daily practice in the Netherlands. METHODS: Subjects aged ≥18 years with a pharmacy prescription of varenicline, bupropion, nicotine replacement therapy (NRT) or nortriptyline between March 2007 and September 2008 were identified from the PHARMO data warehouse, which includes drug dispensing, hospitalisation and other data from approximately 2.5 million residents in the Netherlands. Using an encrypted methodology, corresponding non-person-identifiable dispensing IDs were linked to a web-based system for patient-reported data collection. Corresponding pharmacists asked the subjects to participate in the study and complete a web-based questionnaire on smoking history and cessation, including utilisation of (pharmaco) therapies. RESULTS: Of 2,684 invited subjects, 698 responded (26%), of whom 612 were included in the analyses. Bupropion was the most frequently used smoking cessation drug (35% of patients), followed by varenicline (28%), bupropion + NRT (12%) and varenicline + NRT (9%). Overall, 51% of patients also reported behavioural therapy. A total of 53% of bupropion users, 51% of varenicline users, 42% of NRT users and 20-40% of patients using multiple drugs reported to not smoke at the time of questionnaire. Median (interquartile range) number of days between time of questionnaire and start date of last quit attempt ranged from 271 (104-432) for varenicline + bupropion to 356 (205-518) for bupropion. Mean duration of drug use ranged from 42 to 53 days among quitters and from 19 to 42 days among relapsers. CONCLUSION: In this study up to 50% of patients who obtained smoking cessation drugs at the pharmacy stopped smoking. Better access to smoking cessation drugs as recommended in guidelines will help to further decrease smoking prevalence.