Buprenorphine-naloxone vs. extended-release naltrexone for opioid use disorder in individuals with and without criminal legal involvement: A secondary analysis of the X:BOT randomized controlled trial.

There is uncertainty about whether criminal legal involvement (CLI) impacts the effectiveness of medications for opioid use disorder (MOUD). We aimed to determine whether CLI modifies the association between buprenorphine-naloxone (BUP-NX) vs. extended-release naltrexone (XR-NTX) and MOUD treatment outcomes. We conducted a secondary analysis of X:BOT, a 24-week multi-center randomized controlled trial comparing treatment outcomes between BUP-NX (n = 287) and XR-NTX (n = 283) in the general population. We used baseline Additional Severity-Index Lite responses to identify patients with recent CLI (n = 342), defined as active CLI and/or CLI in the past 30 days, and lifetime incarceration (n = 328). We explored recent CLI and lifetime incarceration as potential effect modifiers of BUP-NX vs. XR-NTX effectiveness on relapse, induction, and overdose. We conducted both intention-to-treat and per-protocol analyses for each outcome. In intention-to-treat analyses, recent CLI modified the effect of BUP-NX vs. XR-NTX on odds of successful induction (p = 0.03) and hazard of overdose (p = 0.04), but it did not modify the effect on hazard of relapse (p = 0.23). All participants experienced lower odds of successful induction with XR-NTX compared to BUP-NX, but the relative likelihood of successful induction with BUP-NX was lower than XR-NTX among individuals with recent CLI (OR: 0.25, 95 % CI: 0.13-0.47, p < 0.001) compared to those without recent CLI (OR: 0.04, 95 % CI: 0.01-0.19, p < 0.001). Participants with recent CLI experienced similar hazard of overdose with XR-NTX and BUP-NX (HR: 1.12, 95 % CI: 0.42-3.01, p = 0.82), whereas those without recent CLI experienced greater hazard of overdose with XR-NTX compared to BUP-NX (HR: 12.60, 95 % CI: 1.62-98.03, p = 0.02). In per-protocol analyses, recent CLI did not modify the effect of MOUD on hazard of overdose (p = 0.10) or relapse (p = 0.41). Lifetime incarceration did not modify any outcome. Compared to individuals without recent CLI, individuals with recent CLI experienced decreased relative effectiveness of BUP-NX compared to XR-NTX for induction and overdose outcomes. This highlights the importance of considering the impact of recent CLI on opioid use disorder treatment outcomes. Future research should explore the mechanisms through which recent CLI modifies MOUD effectiveness and aim to improve MOUD effectiveness for individuals with recent CLI.

Balter DR ，Puglisi LB ，Dziura J ，Fiellin DA ，Howell BA ... -  《-》

Exemplar Hospital Initiation Trial to Enhance Treatment Engagement (EXHIT ENTRE): protocol for CTN-0098 an open-label randomized comparative effectiveness trial of extended-release buprenorphine versus treatment as usual on post-hospital treatment engagem

Hospitalizations involving opioid use disorder (OUD) are increasing. Addiction consultation services (ACS) initiate medications for opioid use disorder (MOUD) in hospital settings and arrange post-hospital follow-up for ongoing MOUD care. Engagement in MOUD following hospital discharge is hampered by challenges in timely access to MOUD. This protocol describes an open-label randomized comparative effectiveness trial comparing ACS treatment as usual (TAU) to a single injection of a 28-day formulation extended-release buprenorphine (XR-BUP) on MOUD engagement 34-days following hospital discharge. Six U.S. hospitals with ACS capable of prescribing all MOUD (i.e., methadone, buprenorphine, and extended-release naltrexone) recruit and randomize hospitalized patients with OUD who have not been on MOUD in the fourteen days prior to hospitalization. TAU may consist of any MOUD other than XR-BUP. Participants randomized to XR-BUP may receive any MOUD throughout their hospital stay and receive a 28-day XR-BUP injection within 72-hours of anticipated hospital discharge. There is no intervention beyond hospital stay. Participants are followed 34-, 90-, and 180-days following hospital discharge. The primary outcome is engagement in any MOUD 34-days following hospital discharge, which we hypothesize will be greater in the XR-BUP group. Randomizing 342 participants (171 per arm) provides 90% power to detect difference in the primary outcome between groups with an odds ratio of 2.1. Safety, secondary, and exploratory outcomes include: adverse events, MOUD engagement on days 90 and 180, opioid positive urine drug tests, self-reported drug use, hospital readmissions and emergency department visits, use of non-opioid drugs, fatal and non-fatal opioid overdose, all-cause mortality, quality of life, and cost-effectiveness. Data are analyzed by intention-to-treat, with pre-planned per-protocol and other secondary analyses that examine gender as an effect modifier, differences between groups, and impact of missingness. Engagement in MOUD care following hospitalization in individuals with OUD is low. This randomized comparative effectiveness trial can inform hospital ACS in medication selection to improve MOUD engagement 34-days following hospital discharge. NCT04345718.

Bart G ，Barth KS ，Baukol P ，Enns E ，Ghitza UE ，Harris J ，Jelstrom E ，Liebschutz JM ，Magane KM ，Voronca D ，Weinstein ZM ，Korthuis PT ... -  《-》

Medications for opioid use disorder: Predictors of early discontinuation and reduction of overdose risk in US military veterans by medication type.

This study: (1) estimated the effect of early discontinuation of medication for opioid use disorder (MOUD) on overdose probability and (2) measured the relationship between patient characteristics and early discontinuation probability for each MOUD type. This was a retrospective cohort using electronic health record data from the US Veterans Healthcare Administration. Participants were veterans initiating MOUD with buprenorphine (BUP), methadone (MET) or extended-release naltrexone (XR-NTX) from fiscal years 2012-19. A total of 39 284 veterans met eligibility with 22 721 (57.8%) initiating BUP, 12 652 (32.2%) initiating MET and 3911 (10.0%) initiating XR-NTX. Measurements (1) determined whether the veteran experienced an overdose in the 365 days after MOUD initiation (primary) and (2) early discontinuation of MOUD, defined as discontinuation before 180 days (secondary). We assumed that unobserved patient characteristics would jointly influence the probability of discontinuation and overdose. and estimated the joint distribution with a bivariate probit model. We found that 9.0% of BUP initiators who experienced an overdose above the predicted 3.9% had no veteran-discontinued BUP early; findings for XR-NTX were similar, with 12.2% of initiators overdosing above the predicted 4.5%, but this was statistically inconclusive. We found no relationship between early discontinuation and overdose for MET initiators, probably due to the high risk of both events. The patient characteristics included in our post-estimation exploratory analysis of early discontinuation varied by MOUD type, with between 14 (XR-NTX) and 25 (BUP) tested. The only characteristics with at least one level showing a statistically significant change in probability of early discontinuation for all three MOUD types were geography and prior-year exposure to psychotherapy, although direction and magnitude varied. Early discontinuation of buprenorphine, and probably extended-release naltrexone, appears to be associated with a greater probability of experiencing a fatal or non-fatal overdose among US veterans receiving medication for opioid use disorder (MOUD); methadone does not show the same association. There is no consistent set of characteristics among early discontinuers by MOUD type.

Hayes CJ ，Raciborski RA ，Nowak M ，Acharya M ，Nunes EV Jr ，Winhusen TJ ... -  《-》

Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use: A Post Hoc Analysis of a Randomized Clinical Trial.

Nunes EV ，Comer SD ，Lofwall MR ，Walsh SL ，Peterson S ，Tiberg F ，Hjelmstrom P ，Budilovsky-Kelley NR ... -  《JAMA Network Open》

Associations between stimulant use and return to illicit opioid use following initiation onto medication for opioid use disorder.

Foot C ，Korthuis PT ，Tsui JI ，Luo SX ，Chan B ，Cook RR ... -  《-》