Faculty Bibliography

BACKGROUND AND AIMS/OBJECTIVE:In a US randomized-effectiveness trial comparing extended-release naltrexone (XR-NTX) with buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse among participants recruited during inpatient detoxification (CTN-0051), the requirement to complete opioid detoxification prior to initiating XR-NTX resulted in lower rates of initiation of XR-NTX (72% XR-NTX versus 94% BUP-NX). DESIGN/METHODS:This was a retrospective secondary analysis of CTN-0051 trial data, including follow-up data over 24-36 weeks. SETTING/METHODS:Eight community-based, inpatient-detoxification and follow-up outpatient treatment facilities in the United States. PARTICIPANTS/METHODS:A total of 283 participants randomized to receive XR-NTX. MEASUREMENTS/METHODS:Efficiency was estimated using a multivariable generalized structural equation model to explore simultaneous determinants of XR-NTX induction and induction duration (detoxification + residential days). Cost-effectiveness was estimated from the health-care sector perspective and included expected costs and quality-adjusted life-years (QALYs). FINDINGS/RESULTS:Treatment site was the only modifiable factor that simultaneously increased the likelihood of XR-NTX induction and decreased induction duration. Incorporating the higher predicted probability of XR-NTX induction, and fewer predicted days of detoxification and subsequent residential treatment into the cost-effectiveness framework, reduced the incremental average 24-week total cost of XR-NTX treatment from $5317 more than that of BUP-NX (P = 0.01) to a non-statistically-significant difference of $1016 (P = 0.63). QALYs gained remained similar across arms. CONCLUSION/CONCLUSIONS:Adopting an efficient model of extended-release naltrexone initiation could result in extended-release naltrexone and buprenorphine-naloxone being of comparable economic value from the health-care sector perspective over 24-36 weeks for patients seeking treatment for opioid use disorder at an inpatient detoxification facility.

Importance/UNASSIGNED:Extended-release buprenorphine (XRB), a monthly injectable long-acting opioid use disorder (OUD) treatment, has not been studied for use in corrections facilities. Objective/UNASSIGNED:To compare treatment retention following release from jail among adults receiving daily sublingual buprenorphine-naloxone (SLB) vs those receiving XRB. Design, Setting, and Participants/UNASSIGNED:This open-label, randomized comparative effectiveness study included 52 incarcerated adults in New York City observed for 8 weeks postrelease between June 2019 and May 2020. Participants were soon-to-be-released volunteers from 1 men's and 1 women's jail facility who had OUDs already treated with SLB. Follow-up treatment was received at a primary care clinic in Manhattan. Data were analyzed between June 2020 and December 2020. Interventions/UNASSIGNED:XRB treatment was offered prior to release and continued monthly through 8 weeks after release. SLB participants continued to receive daily directly observed in-jail SLB administration, were provided a 7-day SLB supply at jail release, and followed up at a designated clinic (or other preferred clinics). Main Outcomes and Measures/UNASSIGNED:Buprenorphine treatment retention at 8 weeks postrelease. Results/UNASSIGNED:A total of 52 participants were randomized 1:1 to XRB (26 participants) and SLB (26 participants). Participants had a mean (SD) age of 42.6 (10.0) years; 45 participants (87%) were men; and 40 (77%) primarily used heroin prior to incarceration. Most participants (30 [58%]) reported prior buprenorphine use; 18 (35%) reported active community buprenorphine treatment prior to jail admission. Twenty-one of 26 assigned to XRB received 1 or more XRB injection prior to release; 3 initiated XRB postrelease; and 2 did not receive XRB. Patients in the XRB arm had fewer jail medical visits compared with daily SLB medication administration (mean [SD] visits per day: XRB, 0.11 [0.03] vs SLB, 1.06 [0.08]). Community buprenorphine treatment retention at week 8 postrelease was 18 participants in the XRB group (69.2%) vs 9 in the SLB group (34.6%), and rates of opioid-negative urine tests were 72 of 130 tests in the XRB group (55.3%) and 50 of 130 tests in the SLB group (38.4%). There were no differences in rates of serious adverse events, no overdoses, and no deaths. Conclusions and Relevance/UNASSIGNED:XRB was acceptable among patients currently receiving SLB, and patients had fewer in-jail clinic visits and increased community buprenorphine treatment retention when compared with standard daily SLB treatment. These results support wider use and further study of XRB as correctional and reentry OUD treatment. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03604159.

The EXIT-CJS (N = 1005) multisite open-label randomized controlled trial will compare retention and effectiveness of extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX) to treat opioid use disorder (OUD) among criminal justice system (CJS)-involved adults in six U.S. locales (New Jersey, New York City, Delaware, Oregon, Connecticut, and New Hampshire). With a pragmatic, noninferiority design, this study hypothesizes that XR-B (n = 335) will be noninferior to XR-NTX (n = 335) in retention-in-study-medication treatment (the primary outcome), self-reported opioid use, opioid-positive urine samples, opioid overdose events, and CJS recidivism. In addition, persons with OUD not eligible or interested in the RCT will be recruited into an enhanced treatment as usual arm (n = 335) to examine usual care outcomes in a quasi-experimental observational cohort.

Buprenorphine, an effective treatment for opioid use disorder (OUD), remains underutilized in many U.S. jails and prisons. However, use of non-prescribed (i.e., diverted) buprenorphine has been reported in these settings. The current study examined non-prescribed buprenorphine use experiences in correctional and community contexts. The study conducted face-to-face interviews with 300 adults with OUD/opioid misuse and recent incarceration, recruited in Baltimore, MD, and New York, NY (n = 150 each). Illicit/non-prescribed opioid use during incarceration was reported by 63% of participants; 39% reported non-prescribed buprenorphine. Non-prescribed buprenorphine was considered the most widely available opioid in jails/prisons in both states (81% reported "very" or "somewhat" easy to get). The average price of non-prescribed buprenorphine in jail/prison was ~10× higher than in the community (p < 0.001). Participants were more likely to endorse getting high/mood alteration as reasons for using non-prescribed buprenorphine during incarceration, but tended to ascribe therapeutic motives to use in the community (e.g., self-treatment; p < 0.001). Multivariable logistic regression analyses showed that different individual-level characteristics were associated with history of non-prescribed buprenorphine use during incarceration and in the community. Use of non-prescribed buprenorphine during incarceration was associated with younger age (p = 0.006) and longer incarceration history (p < 0.001), while use of non-prescribed buprenorphine in the community was associated with MD recruitment site (p = 0.001), not being married (p < 0.001), prior buprenorphine treatment experience (p < 0.001), and housing situation (p = 0.01). These findings suggest that different dynamics and demand characteristics underlie the use of non-prescribed buprenorphine in community and incarceration contexts, with implications for efforts to expand OUD treatment in correctional settings.

OBJECTIVE:Sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments, with distinct mechanisms, for opioid use disorder. The authors examined whether patients' demographic and clinical characteristics were associated with better response to one medication or the other. METHODS:In a multisite 24-week randomized comparative-effectiveness trial of assignment to buprenorphine-naloxone (N=287) compared with extended-release naltrexone (N=283) comprising inpatients planning to initiate medication treatment for opioid use disorder, 50 demographic and clinical characteristics were examined as moderators of the effect of medication assignment on relapse to regular opioid use and failure to initiate medication. Moderator-by-medication interactions were estimated using logistic regression with correction for multiple testing. RESULTS:In the intent-to-treat sample, patients who reported being homeless had a lower relapse rate if they were assigned to receive extended-release naltrexone (51.6%) compared with buprenorphine-naloxone (70.4%) (odds ratio=0.45, 95% CI=0.22, 0.90); patients who were not homeless had a higher relapse rate if they were assigned to extended-release naltrexone (70.9%) compared with buprenorphine-naloxone (53.1%) (odds ratio=2.15, 95% CI=1.44, 3.21). In the subsample of patients who initiated medication, the interaction was not significant, with a similar pattern of lower relapse with extended-release naltrexone (41.4%) compared with buprenorphine (68.6%) among homeless patients (odds ratio=0.32, 95% CI=0.15, 0.68) but less difference among those not homeless (extended-release naltrexone, 57.2%; buprenorphine, 52.0%; odds ratio=1.24, 95% CI=0.80, 1.90). For failure to initiate medication, moderators were stated preference for medication (failure was less likely if the patient was assigned to the medication preferred), parole and probation status (fewer failures with extended-release naltrexone for those on parole or probation), and presence of pain and timing of randomization (more failure with extended-release naltrexone for patients endorsing moderate to severe pain and randomized early while still undergoing medically managed withdrawal). CONCLUSIONS:Among patients with opioid use disorder admitted to inpatient treatment, homelessness, parole and probation status, medication preference, and factors likely to influence tolerability of medication initiation may be important in matching patients to buprenorphine or extended-release naltrexone.

Background/UNASSIGNED:We explored characteristics and beliefs associated with e-cigarette use patterns among cigarette smokers requiring inpatient detoxification for opioid and/or alcohol use disorder(s). Methods/UNASSIGNED:-test statistics, and logistic regression models were used. Results/UNASSIGNED: Conclusions/UNASSIGNED:E-cigarette use seems to be appealing to a small proportion of cigarette smokers with SUD. Although, dual smokers seem to use e-cigarettes for its cessation premise, they don't appear to be actively seeking to quit. E-cigarettes may offer a more effective method for harm reduction, further evaluation of incorporating it within smoking cessation protocols among patients in addiction treatment is needed.

BACKGROUND:Extended-release naltrexone (XR-NTX) is an effective maintenance treatment for opioid use disorder, but induction from active opioid use is a challenge as individuals must complete detoxification before induction. We aimed to determine whether use of methadone or buprenorphine, long acting agonist opioids commonly used for detoxification, were associated with decreased likelihood of induction onto XR-NTX. METHODS:We performed a secondary analysis of a large open-label randomized trial of buprenorphine versus XR-NTX for treatment of individuals with opioid use disorder recruited from eight short term residential (detoxification) units. This analysis only included individuals randomized to the XR-NTX arm of the trial (N = 283). The method of detoxification varied according to usual practices at each inpatient program. Logistic regression models estimating the log-odds of induction onto XR-NTX were fit, with detoxification regimen received as the predictor. RESULTS:In the unadjusted logistic regression model, detoxification drug received (either methadone or buprenorphine) was significantly associated with decreased likelihood of induction onto XR-NTX compared to receiving non-opioid detoxification (Overall: P < 0.001); buprenorphine vs non-opioid detoxification: OR (95% CI) = 0.32 (0.15-0.67); methadone vs non-opioid detoxification: OR (95% CI) = 0.23 (0.11-0.46). After controlling for site as a random effect, the association of detoxification drug with induction success lost statistical significance. CONCLUSIONS:Use of agonist medication during detoxification was associated with XR-NTX induction failure. Medication choice was determined by each site's clinical practice and therefore this association could not be separated from other site level variables. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT02032433.

This activity is a paper presentation on a secondary analysis of factors associated with opioid abstinence three months following the treatment trial. While abstinence is not required for improvement in opioid use outcomes, better understanding of abstinence-related factors can inform efforts to facilitate stable recovery for opioid-dependent individuals. XXBackground(s): Opioid use disorder (OUD) is associated with substantial mortality. There are effective treatments in reducing opioid use and overdose events. However, many patients that successfully initiate OUD pharmacotherapy will discontinue treatment within the first few weeks or months. Upon treatment discontinuation, patients are at risk for relapse and overdose, however, not all patients relapse. There is a need to better understand predictors of relapse and abstinence after medication discontinuation. XXObjective(s): 1) Demonstrate general understanding of effective treatments for OUD and current barriers to treatment retention. 2) Describe factors associated with opioid abstinence from this secondary analysis. 3) Identify limitations in analyses and interpreting results. XXMethod(s): This secondary analysis examines correlates of opioid abstinence in 428 participants at week 36 follow-up from the National Drug Abuse Treatment Clinical Trials Network CTN-0051) X:BOT trial. X:BOT randomized participants to buprenorphine-naloxone (BUP-NX) or extended-release injectable naltrexone (XR-NTX) for up to 24 weeks of outpatient treatment. Study medications were discontinued at study completion or relapse. Follow-up assessments in the community were done at weeks 28 and 36. XXResult(s): Participants had higher odds of being abstinent at week 36 if randomized to XR-NTX compared with BUP-NX (odds ratio [OR] [95% confidence interval [CI]] = 2.47 [1.63, 3.74]), were on XR-NTX at follow-up compared with those off medication (OR = 2.33 [1.40, 3.90]), had longer time to relapse (OR = 1.04 [1.02, 1.07]), successfully inducted onto study medication compared with those who failed induction (OR = 3.16 [1.45, 6.92]), had longer time on study medication (OR = 1.03[1.01, 1.05]), and had more abstinent weeks during the trial (OR = 1.04 [1.02, 1.07]). XXConclusion(s): In general, participants that had better outcomes during the treatment trial were found to be abstinent from opioids at follow-up in the community. This included successful induction onto study medication, longer time on medication, greater time to relapse, and more abstinent weeks. While abstinence is not required for improvement in opioid use outcomes, better understanding of abstinence-related factors can inform efforts to facilitate stable recovery for opioid-dependent individuals. Scientific Significance: There is a need to better understand predictors of relapse and abstinence after medication discontinuation in order to better advise patients that may discontinue medications. Barriers to treatment retention and sustained abstinence are factors generally considered to be proxies for greater disease severity. Less is understood about factors associated with sustained abstinence

AIM/OBJECTIVE:This report examined naturalistic opioid use outcomes and utilization of medications for opioid use disorder (MOUD) 36 weeks post-randomization in the National Drug Abuse Treatment Clinical Trials Network (CTN) Extended-Release Naltrexone (XR-NTX) versus Buprenorphine-Naloxone (BUP-NX) for Opioid Treatment trial (CTN-0051, X:BOT). DESIGN/METHODS:X:BOT was a multisite, randomized, 24-week comparative effectiveness trial of BUP-NX (N = 287) and XR-NTX (N = 283). Study medications were discontinued following treatment completion, relapse, or dropout. Participants were encouraged to continue MOUD. This report examined opioid use outcomes in 428 (75%) of the 570 participants who attended the 36-week follow-up visit. SETTING AND PARTICIPANTS/METHODS:Adults with opioid use disorder recruited from 8 community treatment programs across the United States. MEASUREMENTS/METHODS:Outcomes included medication status (on/off MOUD), type of MOUD (BUP-NX, XR-NTX, or methadone), abstinence from non-prescribed opioids, opioid use days, relapse, and other substance use 30 days prior to the 36-week visit. Relapse was defined as opioid use for 4 consecutive weeks or 7 consecutive days in the past month. Baseline and clinical variables included opioid use severity, intravenous drug use, study medication assignment, and induction status. FINDINGS/RESULTS:Of the 428 participants who completed the 36-week visit, 225 (53%) of participants were receiving MOUD and 203 (47%) were not. Compared to those off medication, participants on medication had fewer opioid use days (4.4 days (SD 9.0) versus 9.8 days (SD 12.1)), fewer met relapse criteria (37 (16.4%) versus 79 (38.9%)), and reported less stimulant use (34 (15.2%) versus 56 (27.7%)) and sedative use (14 (6.3%) versus 31 (15.3%)). There was no difference in abstinence rates between those on or off MOUD. A greater proportion of participants on XR-NTX (47 (53.4%) of 88 participants) were abstinent from non-prescribed opioids compared to those on buprenorphine (28 (23.3%) of 120 participants). CONCLUSIONS:Naturalistic outcomes data showed that despite potential barriers to continuing treatment in the community, about half of individuals were on opioid use disorder pharmacotherapy at follow-up and those on medication generally had better outcomes. Future research should explore barriers and facilitators to treatment retention in community settings; and developing interventions tailored to improve treatment engagement and adherence.