The Effect of Opioid Agonist Treatment on Injection-Related Sequelae: A Population-Based Observational Study

Drug Saf. 2025 Nov;48(11):1271-1280. doi: 10.1007/s40264-025-01574-1. Epub 2025 Jul 3.

Abstract

Introduction: Opioid agonist treatment (OAT) reduces drug-related poisonings and injection-related infections among people with opioid use disorder (OUD). Despite buprenorphine-naloxone (BNX) and methadone (MET) both being first-line OAT options in Canada, their comparative effectiveness in preventing recurrent injection-related infections and poisonings remains unclear.

Objectives: This study compared the effectiveness of buprenorphine-naloxone and methadone in reducing recurrent risks of injection-related bacterial infections and opioid-related poisoning among people on OAT.

Methods: We used administrative health data from Québec, Canada to create our cohort of adult patients (aged 18-65 years) on OAT maintenance between 2014 and 2019. We applied a time-dependent Cox proportional hazards model for our time-varying exposure definition to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the recurrent risks of injection-related bacterial infections and opioid-related poisoning, adjusting for age, sex, socio-demographic, and clinical factors. We also compared the effectiveness of buprenorphine-naloxone and methadone during the OAT induction phase (i.e., first 30 days of treatment).

Results: The study population included 2010 patients (mean age: 41.21 years, 67.41% male). Compared to methadone, buprenorphine-naloxone was associated with 45% lower recurrent risk of opioid-related poisoning (HR: 0.55; 95% CI 0.35-0.86). Overall, the association between buprenorphine-naloxone and recurrent risk of injection-related bacterial infections suggested a weak protective effect (HR: 0.80; 95% CI 0.59-1.09). During the induction phase, there was limited evidence of differences between buprenorphine-naloxone and methadone for the recurrent risks of injection-related bacterial infections (HR: 0.91; 95% CI 0.51-1.60) and opioid-related poisoning (HR: 1.07; 95% CI 0.51-2.24).

Conclusion: Among patients in OAT maintenance, buprenorphine-naloxone was associated with lower risk of recurrent opioid-related poisoning compared to methadone, but not for injection-related infections. This advantage was not observed during induction, suggesting the need for improved treatment retention early in OAT.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analgesics, Opioid* / administration & dosage
  • Analgesics, Opioid* / adverse effects
  • Bacterial Infections* / epidemiology
  • Bacterial Infections* / prevention & control
  • Buprenorphine, Naloxone Drug Combination* / administration & dosage
  • Buprenorphine, Naloxone Drug Combination* / therapeutic use
  • Female
  • Humans
  • Male
  • Methadone* / administration & dosage
  • Methadone* / therapeutic use
  • Middle Aged
  • Narcotic Antagonists / administration & dosage
  • Opiate Substitution Treatment* / methods
  • Opioid-Related Disorders* / drug therapy
  • Opioid-Related Disorders* / epidemiology
  • Quebec / epidemiology
  • Substance Abuse, Intravenous* / epidemiology
  • Young Adult

Substances

  • Methadone
  • Buprenorphine, Naloxone Drug Combination
  • Analgesics, Opioid
  • Narcotic Antagonists