Assessment of Racial Differences in Pharmacotherapy Efficacy for Smoking Cessation

Abstract

IMPORTANCE Understanding Black vs White differences in pharmacotherapy efficacy and the underlying reasons is critically important to reducing tobacco-related health disparities.OBJECTIVE To compare pharmacotherapy efficacy and examine variables to explain Black vs White differences in smoking abstinence. DESIGN, SETTING, AND PARTICIPANTSThis study is a secondary analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) double-blind, placebo-controlled, randomized clinical trial, which took place at clinical trial centers, academic centers, and outpatient clinics in 29 states in the US. US Black and White smokers who smoked 10 or more cigarettes per day with and without psychiatric comorbidity were enrolled between November 2011 and January 2015. Data analysis was performed from July 2019 to January 2020. INTERVENTIONS Participants were randomized (1:1:1:1) in a double-blind, triple-dummy, placeboand active-controlled (nicotine patch) trial of varenicline and bupropion for 12 weeks with follow-up through week 24. MAIN OUTCOMES AND MEASURES Biochemically verified continuous cigarette abstinence rate (CAR) from weeks 9 to 24. Baseline, postbaseline treatment, and safety characteristics were examined as variables to explain race differences in abstinence. RESULTS Of the 1065 Black smokers enrolled, 255 were randomized to receive varenicline, 259 received bupropion, 286 received nicotine replacement therapy (NRT [ie, nicotine patch]), and 265 received placebo. Among the 3044 White smokers enrolled, 778 were randomized to receive varenicline, 769 received bupropion, 738 received NRT, and 759 received placebo. Participants were predominantly female (614 Black [57.7%] and 1786 White [58.7%] women) and heavy smokers (mean [SD] cigarettes per day, 18.2 [7.9] for Black and 20.0 [7.5] for White smokers), with a mean (SD) age of 47.2 (11.2) years for Black and 46.5 (12.7) years for White participants. Treatment and racewere associated with CAR for weeks 9 to 24. The CAR was 4.9% lower for Black vs White participants (odds ratio [OR], 0.53; 95% CI, 0.41-0.69; P < .001); differences were found across all treatments.

Smoking, race, ancestry and prospective abstinence

“…Therefore, we expected to observe a significant reduction in abstinence in African American smokers in the Pharmacogenetic Study. The range of standardized effect estimates we observed, from ORs (95%CI) of 0.31 (0.14-0.69) in the CPD model to 0.34 (0.15-0.74) in the uNMR model, encompass estimates from studies with a variety of designs: randomized on gender and OMB race 42 , stratified by OMB race 6 , or stratified by psychiatric diagnosis 8 .…”

“…The copyright holder for this this version posted December 27, 2021. ; https://doi.org/10.1101/2021.12.24.21267950 doi: medRxiv preprint 5 Nollen et al identified cessation disparities and explanatory factors in analyses of US smokers in the randomized placebo-controlled trial called "Evaluating Adverse Events in a Global Smoking Cessation Study" (EAGLES, NCT01456936) 8,9 . EAGLES was designed to test the relative neuropsychiatric risks and efficacy of varenicline and bupropion to those of nicotine replacement therapy (NRT) and placebo; a total of N=8144 smokers (>=10 cigarettes per day, CPD) with and without psychiatric disorders were enrolled 9 .…”

“…Initial analyses demonstrated no significant increase in neuropsychiatric adverse events due to varenicline or bupropion compared to NRT or placebo, or across diagnostic cohorts; greatest effectiveness was observed with varenicline, and with bupropion and NRT versus placebo. In analyses of data from N=4109 US EAGLES participants (25.9% Black and 74.1% White) 8 , Nollen et al examined treatment group, psychiatric cohort, and race stratified groups for association with abstinence, then examined 41 participant and trial characteristics for association with race and with abstinence, and constructed a best joint model of abstinence. They observed reduced abstinence over all treatments and diagnostic cohorts in Black participants when compared to White participants (OR=0.53 (0.41-0.69) P<.001).…”

“…From 19 participant and trial characteristics associated with both race and abstinence, the final abstinence model retained six baseline variables (age, race, anxiety, Fagerström Test for Nicotine Dependence (FTND), CPD, and lifetime quit attempts) and three trial variables (study drug discontinuation, depression score change and emergent adverse events). These analyses have provided evidence that the social construct of race, and demographic, psychometric, smoking, socioeconomic and treatment measures are associated with cessation disparities 8,9 .…”

“…The primary outcome was continuous abstinence CPD, and lifetime quit attempts) and three trial variables (study drug discontinuation, depression score change and emergent adverse events). These analyses have provided evidence that the social construct of race, and demographic, psychometric, smoking, socioeconomic and treatment measures are associated with cessation disparities 8,9 .…”