Population-Level Health Benefits and Harms Associated With Buprenorphine/Naloxone vs Methadone.

Abstract

In 2017, British Columbia guidelines changed the preferred first-line treatment for opioid use disorder from methadone to buprenorphine/naloxone. Systematic reviews have consistently shown better treatment retention associated with methadone, while studies have reported a reduced risk of mortality associated with buprenorphine/naloxone, causing confusion in interpretation for clinical guidelines. To estimate the population-level health benefits and harms associated with buprenorphine/naloxone vs methadone for treatment of opioid use disorder, accounting for differences in treatment retention and risk of mortality while receiving treatment. This decision analytic model analysis was conducted from January 1, 2010, to March 17, 2020, using a semi-Markov cohort model and linked population-level health administrative data on all individuals presenting for opioid agonist treatment in British Columbia, Canada. Hazard ratios were estimated for the association of buprenorphine/naloxone vs methadone with treatment discontinuation (breaks in dispensations lasting ≥5 days for methadone and ≥6 days for buprenorphine/naloxone) and mortality while receiving treatment (per protocol). Treatment episodes in primary analysis were based on the medication initiated (initiator analysis). Probabilistic (mean estimates and 95% credible intervals from 10 000 simulations) and deterministic sensitivity analyses were conducted. Data were analyzed between August 2023 and October 2024. Alternative treatment policies in which buprenorphine/naloxone or methadone were exclusively available to individuals presenting for opioid agonist treatment. Incremental life-years, fatal overdoses, and all-cause deaths. The study population included 40 461 individuals with 109 126 cumulative person-years of follow-up (median [IQR] age, 33 [23-43] years; 66.0% [range, 56.0%-76.0%] male). A policy of exclusively buprenorphine/naloxone was estimated to have -1602 incremental life-years (95% credible interval, -3249 to -549 life-years) compared with methadone, with an additional 221 fatal overdoses (95% credible interval, 119 to 376 overdoses) and 303 all-cause deaths (95% credible interval, 120 to 589 deaths) over a 10-year period. Results from this study suggest that any advantages from a reduced risk of mortality with treatment with buprenorphine/naloxone were outweighed by deficits in treatment retention. Evaluated in a jurisdiction where both medications were available in office-based settings, these findings do not support recommendations of buprenorphine/naloxone as first-line treatment over methadone.