Efficacy of bupropion and varenicline genetic markers in choosing pharmacological treatment for smoking cessation, and implications for combining drugs: A randomized controlled trial - GENTSMOKING

Patricia V Gaya; Juliana R Santos; Paulo R X Tomaz; Tania M O Abe; Miguel Nassif Jr; Larissa G Galas; Bianca B Bellini; Iana R Moraes; Paulo C Lima Santos; Paulo C R P Correa; Jaqueline R Scholz

doi:10.18332/tid/186072

Efficacy of bupropion and varenicline genetic markers in choosing pharmacological treatment for smoking cessation, and implications for combining drugs: A randomized controlled trial - GENTSMOKING

Tob Induc Dis. 2024 Apr 16:22. doi: 10.18332/tid/186072. eCollection 2024.

Affiliations

¹ Programa de Tratamento do Tabagismo do Servico de Prevencao e Reabilitacao, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
² Laboratorio de Genetica e Biologia Molecular, Instituto do Coracao, Hospital da Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
³ Departamento de Farmacologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
⁴ Universidade Federal de Ouro Preto, Minas Gerais, Brazil.

Abstract

Introduction: Smoking cessation is the best strategy for reducing tobacco-related morbimortality. The goal of this randomized controlled trial was to test whether using the genetically favorable markers to choose a smoking cessation drug treatment (precision medicine) was superior to using the most effective drug (varenicline) in terms of abstinence rates. Additionally, combination therapy was tested when monotherapy failed.

Methods: This partially blind, single-center study randomized (1:1) 361 participants into two major groups. In the genetic group (n=184), CYP2B6 rs2279343 (genotype AA) participants started treatment with bupropion, and CHRNA4 rs1044396 (genotype CT or TT) participants started treatment with varenicline; when genetic favorable to both, participants started treatment with bupropion, and when favorable to neither, on both drugs. In the control group (n=177), participants started treatment with varenicline, regardless of genetic markers. Drug treatment lasted 12 weeks. Efficacy endpoints were abstinence rates at Weeks 4, and Weeks 8-12, biochemically validated by carbon monoxide in exhaled air. Participants who did not achieve complete abstinence at Week 4, regardless of group, were given the choice to receive combination therapy.

Results: Abstinence rates were 42.9% (95% CI: 36-64) in the control group versus 30.4% (95% CI: 23-37) in the genetic group at Week 4 (p=0.01); and 74% (95% CI: 67-80) versus 52% (95% CI: 49-64) at Week 12 (p<0.001), respectively. The strategy of combining drugs after Week 4 increased abstinence rates in both groups and the significant difference between genetic and control groups was maintained.

Conclusions: Results show that using these selected genetic markers was inferior to starting treatment with varenicline (control group), which is currently the most effective smoking cessation drug; moreover, the addition of bupropion in cases of varenicline monotherapy failure improves the efficacy rate until the end of treatment.

Clinical trial identifier: NCT03362099.

Keywords: bupropion; pharmacogenetics; precision medicine; smoking cessation; varenicline.

Associated data

ClinicalTrials.gov/NCT03362099

Grants and funding

FUNDING The GENTSMOKING Trial (NCT03362099) was funded by FAPESP (Fundaçao Amparo a Pesquisa Estado de São Paulo (Proc. 2013-09295-3 and Proc.2013-20614-3) CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico [Brazilian National Council for Scientific and Technological Development]) [grant number 470410/2013-2].