Prescribing of smoking cessation medication in England since the introduction of varenicline

Aims To estimate the effect of the introduction of a new smoking cessation medication, varenicline, and the publication of guidance related to its use, on trends in prescribing of smoking cessation medications in England. Design Interrupted time series analysis of primary care data on prescribing of smoking cessation medication using autoregressive integrated moving average (ARIMA) modelling. Setting A total of 446 general practices included in The Health Improvement Network (THIN), a database of UK electronic primary care records. Participants All primary care patients registered with a THIN practice in England. Measurements Monthly rates of prescribing of varenicline, nicotine replacement therapy (NRT) and bupropion per 100 000 patients registered with a THIN practice between June 2000 and June 2009. Findings NRT was the most commonly prescribed stop smoking medication, and bupropion the least frequently prescribed. After its introduction in December 2006 varenicline rapidly became the second most commonly prescribed drug. There was no statistically significant change in overall prescribing for smoking cessation medications after its introduction (P = 0.760), or after the publication of the related guidance in July 2007 (P = 0.134). Conclusions Soon after being introduced in England, varenicline was widely prescribed; after nicotine replacement therapy it was the most commonly prescribed cessation medication. However, this does not appear to have increased overall rates of prescribing for smoking cessation medication.     

Combination bupropion SR and varenicline for smoking cessation: a systematic review

ABSTRACT

Background: Tobacco is the leading cause of preventable death in the world. Current cessation medications include nicotine replacement therapy (NRT), varenicline, and bupropion, while combination therapy primarily entails NRT with either varenicline or bupropion. However, recent studies have examined varenicline and bupropion in combination. Objectives: A systematic review assessing the efficacy and safety of combination varenicline and bupropion was conducted. Methods: PubMed and Clinicaltrials.gov were searched using terms: “varenicline combination”, “bupropion combination”, “bupropion AND varenicline”, and “bupropion AND varenicline combination smoking cessation”, yielding four studies including 1193 total patients. Results: Combination therapy yielded greater efficacy than varenicline monotherapy in two randomized controlled trials and one retrospective outcomes study. One single-arm Phase II trial provided additional efficacy and safety data. Of the prospective trials, one displayed a greater 4-week smoking abstinence for weeks 8–11 with combination (39.8%) versus monotherapy (25.9%) (OR = 1.89; 95% CI = 1.07–3.35). The other demonstrated greater prolonged abstinence (continuous abstinence from week 2) at 12 weeks (OR = 1.49; 95% CI = 1.05–2.12) and 26 weeks (OR = 1.52; 95% CI = 1.04–2.22), though results were not significant at 52 weeks in this study. The retrospective study displayed higher success rates (continuous abstinence rates at 52 weeks) with combination varenicline and bupropion (55.0%; compared to varenicline monotherapy (32.1%), p < 0.001). Subgroup analyses suggest that this combination may be more beneficial in males and patients with higher baseline nicotine dependence. Conclusion: To the authors’ knowledge, this is the first review conducted to compile current literature on this novel pharmacotherapy combination for smoking cessation. Combination bupropion SR and varenicline displayed greater efficacy in smoking cessation than varenicline monotherapy, though further safety analysis is warranted to rule out additive psychiatric adverse effects.     

Smoking cessation therapy with varenicline

Smoking cessation is the only available intervention proven to halt progression of chronic obstructive pulmonary disease (COPD). The authors discuss the current existing treatment modalities and the role of a newly approved agent, varenicline, in promotion of smoking cessation. Varenicline is a novel agent that is a centrally acting partial nicotinic acetylcholine receptor agonist. It has both agonistic and antagonistic properties that together are believed to account for reduction of craving and withdrawal as well as blocking the rewarding effects of smoking. Its targeted mechanism of action, better efficacy and tolerability makes varenicline a useful therapeutic option for smoking cessation. In this article, we discuss presently available options for smoking cessation and review the literature on efficacy of varenicline.     

Factors associated with the efficacy of smoking cessation treatments and predictors of smoking abstinence in EAGLES

Aims

To assess (1) how far the efficacies of front‐line smoking cessation pharmacotherapies vary as a function of smoker characteristics and (2) associations between these characteristics and success of smoking cessation attempts.

Design

Prospective correlational study in the context of a double‐blind randomized trial. The outcome was regressed individually onto each covariate after adjusting for treatment, and then a forward stepwise model constructed. Treatment moderator effects of covariates were tested by treatment × covariate interactions.

Setting

Health service facilities in multiple countries.

Participants

Data came from 8120 smokers willing to make a quit attempt, randomized to varenicline, bupropion, nicotine replacement therapy (NRT) or placebo in Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) between 30 November 2011 and 13 January 2015.

Measurements

Smoker characteristics measured at baseline were country, psychiatric history, sex, age, body mass index (BMI), ethnic group, life‐time suicidal ideation/behaviour, anxiety, depression, aggression, psychotropic medication, history of alcohol/substance use disorder, age of starting smoking, cigarette dependence [Fagerström Test for Cigarette Dependence (FTCD)] and prior use of study medicines. Outcome was biochemically confirmed continuous abstinence at weeks 9–24 from start of treatment.

Findings

No statistically significant treatment × covariate interactions were found. Odds of success were associated independently positively with age [odds ratio (OR) = 1.01; 95% confidence interval (CI) = 1.00, 1.01], BMI (1.01; 95% CI = 1.00, 1.02) and age of starting smoking (1.03; 95% CI = 1.02, 1.04). Odds were associated independently negatively with US (versus non‐US) study site (0.53; 95% CI = 0.46, 0.61), black (versus white) ethnic group (0.57; 95% CI = 0.45, 0.72), mood disorder (0.85; 95% CI = 0.73, 0.99), anxiety disorder (0.71; 95% CI = 0.55, 0.90) and psychotic disorder (0.73; 95% CI = 0.50, 1.07), taking psychotropic medication (0.81; 95% CI = 0.68, 0.95), FTCD (0.89; 95% CI = 0.87, 0.92) and previous use of NRT (0.78; 95% CI = 0.67, 0.91).

Conclusions

While a range of smoker characteristics—including psychiatric history, cigarette dependence and prior use of nicotine replacement therapy (NRT)—are associated with lower cessation rates, they do not substantially influence the efficacy of varenicline, bupropion or NRT.     

Ten-year experience of smoking cessation in a single center in Japan

BackgroundLong-term, real-world data, as opposed to academic or research data, on outcomes of smoking cessation clinics are scarce. We assessed patient outcomes over a 10-year period at a smoking cessation clinic in a community teaching hospital in Japan and explored predictors of successful smoking cessation.MethodsWe used data from a prospective registry of cigarette smokers who participated in a 3-month smoking cessation program comprising combined pharmacological treatment and cognitive behavioral therapy and explored factors associated with program execution and successful smoking cessation. The primary outcome was smoking cessation, defined by quitting completely between the 8-week and 12-week sessions, with verification according to exhaled carbon monoxide (CO) level of ≤10 ppm.ResultsBetween August 2007 and December 2017, 813 patients with nicotine dependence participated in the program. The number of participants decreased after Japan׳s 2010 tobacco tax increase. Among participants, 433 (53.3%) completed the program. In multivariate analysis, the number of cigarettes smoked daily (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.96, 0.99), cardiovascular disease (OR 1.75, 95% CI 1.16, 2.68), chronic obstructive pulmonary disease (OR 1.74, 95% CI 1.10, 2.78), and gastric/duodenal ulcer (OR 1.77, 95% CI 1.04, 3.08) were significantly associated with program completion. Among program completers, 288 (66.5%) achieved smoking cessation. Exhaled CO level (OR 0.94, 95% CI 0.93, 0.97) and mental disorders (OR 0.53, 95% CI 0.33, 0.85) were negatively associated with successful smoking cessation.ConclusionsBaseline exhaled CO level and mental disorders were significantly associated with either success or failure of smoking cessation.     

Cost effectiveness of interventions to reduce relapse to smoking following smoking cessation

Aims To determine the incremental cost effectiveness of nicotine replacement therapy (NRT), bupropion and varenicline for preventing relapse to smoking when used by abstinent smokers Design setting and participants Cohort simulation and sensitivity analyses combining cost and health service data with systematic review estimates for the effectiveness of NRT, bupropion and varenicline when used by abstinent quitters to prevent their relapse to smoking. Measurements Incremental health gain in Quality Adjusted Life Years (QALYs) generated by each drug compared to ‘no intervention’. Findings Bupropion resulted in an incremental QALY increase of 0.07 with a concurrent cost saving of £68; NRT and varenicline both caused incremental QALYs increases of 0.04 at costs of £12 and £90 respectively, although varenicline findings were based on data from a single clinical trial and require cautious interpretation. Even after extensive sensitivity analyses with substantial varying of key model parameters, cost effectiveness of all drugs remained. Cost effectiveness ratios only exceeded the UK National Institute of Clinical Excellence (NICE) benchmark of £20 000 per QALY when drug treatment effects were postulated to last for no longer than 1 year; or, for NRT and varenicline, efficacy was reduced to 10% of that observed in clinical trials. Conclusions Bupropion, nicotine replacement therapy and varenicline appear cost effective at preventing relapse to smoking by smokers who are in quit attempts and have recently become abstinent; they have comparable cost effectiveness to smoking cessation interventions. Widespread use of these effective relapse prevention treatments could promote substantial health gain at an acceptable cost to health providers.