Comparative effectiveness of alternative times to opioid agonist treatment taper initiation on taper completion and all-cause mortality among people with opioid use disorder: A retrospective population-based target trial emulation study in British Columbia, Canada, 2010-2020

Abstract

Background and Aims: Opioid use disorder (OUD) treatment guidelines worldwide recommend opioid agonist treatment (OAT) as a long-term, potentially indefinite treatment for managing OUD. However, many individuals express a strong interest in eventually tapering fully off treatment. Current clinical practice guidelines offer relatively limited guidance or evidence on the appropriate timing to initiate a taper. We aimed to determine the safety and comparative effectiveness of different times from completion of OAT induction at which tapering could be considered to maximize the likelihood of taper completion and minimize the risk of mortality. Design: Population-based retrospective observational study and target trial emulation based on nine-linked administrative health databases. Setting: British Columbia, Canada, from 01/01/2010 to 03/17/2020. Participants: Individuals (identified via linkage of nine provincial health administrative databases) completing OAT induction with methadone or buprenorphine/naloxone who were ≥18 years of age with no known pregnancy, no history of cancer or palliative care and not currently incarcerated. We executed both incident-user (no OAT experiences) and prevalent-new-user (no OAT within the past month) analyses. Intervention and Comparator: The time between completed OAT induction and taper initiation:<3 months, 3-6 months, 6-12 months, compared with 12-48 months. Measurements: The primary outcomes were completed taper (reaching a final daily dose of ≤5mg/day for methadone, or ≤2mg/0.5mg/day for buprenorphine/naloxone) and all-cause mortality. A clone-censor-weight approach was used to adjust for informative censoring and balance baseline characteristics between the groups. Logistic regression and pooled logistic regression models were used to estimate odds ratios (ORs) for completed taper and hazard ratios (HRs) for all-cause mortality, respectively, each with 95% compatibility (“confidence”) intervals. Findings: We included 17,726 incident users (buprenorphine/naloxone: 36.9%) and 49,515 treatment episodes (buprenorphine/naloxone: 31.2%) from 31,231 prevalent new users who completed induction in the analyses. Among prevalent new users, beginning tapering within three months, between 3-6 months and between 6-12 months of completing induction was associated with an increased likelihood of completed taper (methadone:<3 months: adjusted odds ratio [aOR]=3.09 ( 95% confidence interval, 2.58,3.68); buprenorphine/naloxone:<3 months: aOR=6.90 (5.19,9.16)) but a higher risk of mortality (methadone:<3 months: adjusted hazard ratio [aHR]=1.18 (1.12,1.25); buprenorphine/naloxone:<3 months: aHR=1.12 (1.05,1.19)), compared with initiating a taper between 12-48 months. Similar results were found among incident users. Conclusions: Although initiating early tapering off opioid agonist treatment may be associated with a greater likelihood of taper completion, this practice also increases the risk of mortality.