Dataset Information

Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes.

ABSTRACT:

Introduction

Adherence to pharmacotherapies for tobacco dependence, such as varenicline, is necessary for effective treatment. The relationship between varenicline adherence, determined by commonly used indirect (i.e., self-reported pill counts) and infrequently used direct (i.e., varenicline levels) methods, and abstinence outcomes have not been previously examined, nor has their impact on the outcomes of a genetically randomized clinical trial been assessed.

Methods

At Week 1 following target quit date, self-reported pill count and salivary varenicline levels were obtained from participants (N = 376) in a smoking cessation clinical trial (NCT01314001). Point-prevalence abstinence was biochemically-verified by salivary cotinine at Week 1 and by exhaled carbon monoxide at Week 1, end-of-treatment, 6 and 12 months following treatment. Blood nicotine metabolite ratio (NMR) was obtained at baseline.

Results

Adherent individuals based on varenicline levels were significantly more likely to be abstinent than non-adherent individuals at Week 1 (odds ratios [ORs] 1.92-3.16, p's≤0.006), end-of-treatment (OR = 2.53, p = .004), and six months following treatment (OR = 2.30, p = .03). In contrast, pill counts did not consistently predict abstinence. Including direct measures of adherence enhanced the association between rate of nicotine metabolism (NMR) and end-of-treatment abstinence; normal metabolizers (NMR ≥ 0.31) were significantly more likely than slow metabolizers (NMR < 0.31) to be abstinent at end-of-treatment (OR = 2.00, p = .005).

Conclusion

Adherence based on salivary varenicline, rather than on pill counts, is predictive of Week 1 abstinence, irrespective of the biomarker of abstinence assessed, and of long-term abstinence. Direct measures of adherence enhance the ability to assess the impact of a biomarker or genetic marker on abstinence outcomes.

SUBMITTER: Peng AR

PROVIDER: S-EPMC6085881 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes.

Peng Annie R AR Schnoll Robert R Hawk Larry W LW Cinciripini Paul P George Tony P TP Lerman Caryn C Tyndale Rachel F RF

Drug and alcohol dependence 20180626

<h4>Introduction</h4>Adherence to pharmacotherapies for tobacco dependence, such as varenicline, is necessary for effective treatment. The relationship between varenicline adherence, determined by commonly used indirect (i.e., self-reported pill counts) and infrequently used direct (i.e., varenicline levels) methods, and abstinence outcomes have not been previously examined, nor has their impact on the outcomes of a genetically randomized clinical trial been assessed.<h4>Methods</h4>At Week 1 fo ...[more]

PMID: 29986268

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Project description:Background and aimsLevel of adherence to tobacco cessation medication regimens is believed to be causally related to medication effectiveness. This study aimed to evaluate the efficacy of varenicline directly observed therapy (DOT) on varenicline adherence and smoking cessation rates among smokers with opioid use disorder (OUD) receiving methadone treatment.DesignMulticenter, parallel-group two-arm randomized controlled trial.SettingUrban opioid treatment program (OTP) in the Bronx, New York, USA.ParticipantsDaily smokers of ≥ 5 cigarettes/day, interested in quitting (ladder of change score 6-8), in methadone treatment for ≥ 3 months, attending OTP ≥ 3 days/week. Participants' mean age was 49 years, 56% were male, 44% Latino, 30% Black, and they smoked a median of 10 cigarettes/day.InterventionsIndividual, block, random assignment to 12 weeks of varenicline, either directly observed with methadone (DOT, n = 50) or via unsupervised self-administered treatment (SAT, n = 50).MeasurementsThe primary outcome was adherence measured by pill count. The secondary outcome was 7-day point prevalence tobacco abstinence verified by expired carbon monoxide (CO) < 8 parts per million.FindingsRetention at 24 weeks was 92%. Mean adherence was 78.5% [95% confidence interval (CI) = 71.8-85.2%] in the DOT group versus 61.8% in the SAT group (95% CI = 55.0-68.6%); differences were driven by DOT effects in the first 6 weeks. CO-verified abstinence did not differ between groups during the intervention (P = 0.26), but was higher in the DOT than the SAT group at intervention end (DOT = 18% versus SAT = 10%, difference = 8%, 95% CI = -13, 28); this difference was not significant (P = 0.39) and was not sustained at 24-week follow-up.ConclusionsAmong daily smokers attending opioid treatment programs, opioid treatment program-based varenicline directly observed therapy was associated with early increases in varenicline adherence compared with self-administered treatment, but findings were inconclusive as to whether directly observed therapy was associated with a difference in tobacco abstinence.

Project description:Background and aimsVarenicline effectiveness may be related to the level of adherence, which might be reduced by adverse effects such as nausea. The aim of the study was to test a possible effect of nausea on smoking cessation outcomes mediated by adherence.DesignMediation path analysis.SettingMultiple sites within Canada and the United States.ParticipantsTreatment-seeking smokers receiving varenicline from two smoking cessation clinical trials: Quit2Live (NCT01836276; n = 449) and Pharmacogenetics of Nicotine Addiction Treatment (PNAT) (NCT01314001; n = 421).MeasurementsNausea severity was collected through self-report and adherence was biologically assessed using varenicline concentrations (Quit2Live, plasma sample at week 4; PNAT, saliva sample at week 2). In Quit2Live, the end-points were cotinine-verified abstinence at weeks 4, 12 and 26. In PNAT, the end-points were carbon monoxide-verified abstinence at weeks 2, 12 and 26.FindingsEarly nausea was not directly associated with abstinence [odds ratio (OR) ranging from 0.73-1.28; P ≥ 0.26]. However early nausea was indirectly associated with lower cessation rates at multiple timepoints (ORs ranging from 0.92-0.94; 95% CI between 0.83-0.99) in a relationship mediated by reduced varenicline adherence (assessed by plasma varenicline concentrations) in the primary trial (Quit2Live). This relationship between nausea, adherence and cessation was similar in direction but weaker in effect size (ORs ranging from 0.98-0.99; 95% CI between 0.90-1.03) in a secondary trial (PNAT), where adherence was assessed using salivary varenicline concentrations.ConclusionsThese data suggest that early nausea during varenicline treatment may be indirectly associated with lower likelihood of smoking cessation through reducing varenicline adherence. Differences in robustness between the trials may be due to the different biological matrices (plasma vs. saliva) and/or timing used to assess varenicline adherence. The results of the first study suggest that improved management of early nausea during varenicline treatment may positively impact smoking cessation success through increasing varenicline adherence.

Project description:ImportanceEven with varenicline, the leading monotherapy for tobacco dependence, smoking abstinence rates remain low. Preliminary evidence suggests that extending the duration of varenicline treatment before quitting may increase abstinence.ObjectiveTo test the hypotheses that, compared with standard run-in varenicline treatment (1 week before quitting), extended run-in varenicline treatment (4 weeks before quitting) reduces smoking exposure before the target quit date (TQD) and enhances abstinence, particularly among women.Design, setting, and participantsThis double-blind, randomized, placebo-controlled clinical trial enrolled participants from October 2, 2017, to December 9, 2020, at a single-site research clinic in Buffalo, New York. Of 1385 people screened, 320 adults reporting smoking 5 or more cigarettes per day (CPD) were randomized and followed up for 28 weeks. Data were analyzed from August 2021 to June 2022.InterventionsIn the pre-TQD period (weeks 1-4), the extended run-in group received 4 weeks of varenicline; the standard run-in group received 3 weeks of placebo followed by 1 week of varenicline. Both groups received open-label varenicline during weeks 5 to 15 and brief quit counseling at 6 clinic visits.Main outcomes and measuresThe primary outcome consisted of cotinine-verified (at end of treatment [EOT]) self-reported continuous abstinence from smoking (in CPD) during the last 4 weeks of treatment. Secondary outcomes included bioverified self-report of continuous abstinence at the 6-month follow-up and percentage of reduction in self-reported smoking rate during the prequit period (week 1 vs week 4).ResultsA total of 320 participants were randomized, including 179 women (55.9%) and 141 men (44.1%), with a mean (SD) age of 53.7 (10.1) years. Continuous abstinence during the final 4 weeks of treatment (weeks 12-15; EOT) was not greater in the extended run-in group (64 of 163 [39.3%]) compared with the standard run-in group (57 of 157 [36.3%]; odds ratio [OR], 1.13 [95% CI, 0.72-1.78]), nor was the hypothesized group × sex interaction significant (OR, 0.52 [95% CI, 0.21-1.28]). Similar nonsignificant results were obtained for continuous abstinence at the 6-month follow-up. The mean (SE) decrease in self-reported smoking rate during the prequit period was greater in the extended run-in group (-38.8% [2.8%]) compared with the standard run-in group (-17.5% [2.7%]).Conclusions and relevanceAmong adult daily smokers, extending the duration of prequit varenicline treatment beyond the standard 1-week run-in period reduced prequit smoking exposure but, more importantly, did not significantly improve continuous abstinence rates.Trial registrationClinicalTrials.gov Identifier: NCT03262662.

Dataset Information

Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes.

Introduction

Methods

Results

Conclusion

Publications

Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes.

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