Comparative effectiveness of extended‐release naltrexone versus buprenorphine‐naloxone on treatment interruption: Comparing findings from a reanalysis of the X:BOT RCT and harmonized target trial emulation using population‐based observational data
Academic Article
AbstractBackground and aimsIt is unclear if findings from randomized controlled trials (RCT) of medications for opioid use disorder apply to real‐world settings. We estimated the effectiveness of buprenorphine‐naloxone (BUP‐NX) versus extended‐release naltrexone (XR‐NTX) on treatment interruption in a RCT and an observational study based on real‐world data.DesignTarget trial emulation to harmonize the protocol and statistical analyses of X:BOT (target trial) and the observational study (observational emulation). Baseline was randomization in the target trial and medically managed opioid withdrawal (MMOW) discharge in the observational emulation.SettingsX:BOT trial and Massachusetts Public Health Data Warehouse observational data (United States).ParticipantsThe target trial included all X:BOT participants. The observational emulation trial included MMOW discharges from January 2014 to May 2016.MeasurementsTreatment strategies were BUP‐NX versus XR‐NTX initiation within 28 days of baseline. The outcome was treatment interruption (earliest of treatment discontinuation, incarceration, MMOW readmission, death). We estimated the 24‐week risk and risk difference.FindingsIn the target trial, 94% (269/287) and 66% (187/283) of participants randomized to BUP‐NX or XR‐NTX initiated their assigned treatment within 28 days, respectively. In the observational emulation, BUP‐NX and XR‐NTX were initiated within 28 days in 9% (5209/59 076) and 3% (1813/59 076) of MMOW discharges, respectively. The adjusted 24‐week treatment interruption risks (95% confidence interval) for BUP‐NX and XR‐NTX were 68% (60%,77%) and 72% (60%,83%) in the target trial [risk difference, −4 percentage points (pp; −17 pp,11 pp)] and 82% (81%,83%) and 93% (92%,95%) in the observational emulation [risk difference,‐11 pp (−13 pp,‐10 pp)].ConclusionsBuprenorphine‐naloxone might be superior to extended‐release naltrexone in real‐world settings where the majority of people struggle to remain on medications for opioid use disorder. Buprenorphine‐naloxone initiators had a lower risk of treatment interruption than extended‐release naltrexone initiators in an observational emulation, but similar risks in a randomized controlled trial, although confidence intervals were wide. Trial participation, study size and residual confounding may explain these differences.
