Faculty Bibliography

OBJECTIVE:Polysubstance use may complicate treatment outcomes for individuals who use opioids. This research aimed to examine the prevalence of polysubstance use in an opioid use disorder treatment trial population and polysubstance use's association with opioid relapse and craving. METHODS:This study is a secondary data analysis of individuals with opioid use disorder who received at least one dose of medication (n = 474) as part of a 24-week, multi-site, open label, randomized Clinical Trials Network study (CTN0051, X:BOT) comparing the effectiveness of extended-release naltrexone versus buprenorphine. Models examined pretreatment polysubstance use and polysubstance use during the initial 4 weeks of treatment on outcomes of relapse by week 24 of the treatment trial and opioid craving. RESULTS:Polysubstance use was generally not associated with treatment outcomes of opioid relapse and craving. Proportion of days of pretreatment sedative use was associated with increased likelihood of opioid relapse (OR: 1.01, 95 % CI: 1.00-1.02). Proportion of days of cocaine use during the initial 4 weeks of treatment was associated with increased likelihood of opioid relapse (OR: 1.05, 95 % CI: 1.01-1.09) but this effect was no longer significant once the potential of confounding by opioid use was considered. Sedative use during initial 4 weeks of treatment was associated with increased opioid craving (b: 0.77, 95 % CI: 0.01-1.52). The study found no other significant relationships. CONCLUSIONS:In the current study population, polysubstance use was only marginally associated with 24-week treatment outcomes.

PURPOSE/OBJECTIVE:The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP). METHODS:Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines. RESULTS:In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response. CONCLUSION/CONCLUSIONS:These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

BACKGROUND AND AIMS/OBJECTIVE:Dynamic, adaptive pharmacologic treatment for opioid use disorder (OUD) has been previously recommended over static dosing to prevent relapse, and is aligned with personalized medicine. However, there has been no quantitative evidence demonstrating its advantage. Our objective was to estimate the extent to which a hypothetical intervention that increased buprenorphine dose in response to opioid use would affect risk of relapse over 24 weeks of follow-up. DESIGN/METHODS:A secondary analysis of the buprenorphine arm of an open-label randomized controlled 24-week comparative effectiveness trial, 2014-17. SETTING/METHODS:Eight community addiction treatment programs in the United States. PARTICIPANTS/METHODS:English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 270). Participants were mainly white (65%) and male (72%). INTERVENTION(S)/METHODS:Participants were treated with daily sublingual buprenorphine-naloxone (BUP-NX), with dose based on clinical indication, determined by the provider. We examined a hypothetical intervention of increasing dose in response to opioid use. MEASUREMENTS/METHODS:Outcome was relapse to regular opioid use during the 24 weeks of outpatient treatment, assessed in a survival framework. We estimated the relapse-free survival curves of participants under a hypothetical (i.e. counterfactual) intervention in which their BUP-NX dosage would be increased following their own subject-specific opioid use during the first 12 weeks of treatment versus a hypothetical intervention in which dose would remain constant. FINDINGS/RESULTS:We estimated that increasing BUP-NX dose in response to recent opioid use would lower risk of relapse by 19.17 percentage points [95% confidence interval (CI) = -32.17, -6.18) (additive risk)] and 32% (0.68, 95% CI = 0.49, 0.86) (relative risk). The number-needed-to-treat with this intervention to prevent a single relapse is 6. CONCLUSIONS:In people with opioid use disorder, a hypothetical intervention that increases sublingual buprenorphine-naloxone dose in response to opioid use during the first 12 weeks of treatment appears to reduce risk of relapse over 24 weeks, compared with holding the dose constant after week 2.

Importance/UNASSIGNED:Emergency departments (EDs) are increasingly initiating treatment for patients with untreated opioid use disorder (OUD) and linking them to ongoing addiction care. To our knowledge, patient perspectives related to their ED visit have not been characterized and may influence their access to and interest in OUD treatment. Objective/UNASSIGNED:To assess the experiences and perspectives regarding ED-initiated health care and OUD treatment among US patients with untreated OUD seen in the ED. Design, Setting, and Participants/UNASSIGNED:This qualitative study, conducted as part of 2 studies (Project ED Health and ED-CONNECT), included individuals with untreated OUD who were recruited during an ED visit in EDs at 4 urban academic centers, 1 public safety net hospital, and 1 rural critical access hospital in 5 disparate US regions. Focus groups were conducted between June 2018 and January 2019. Main Outcomes and Measures/UNASSIGNED:Data collection and thematic analysis were grounded in the Promoting Action on Research Implementation in Health Services (PARIHS) implementation science framework with evidence (perspectives on ED care), context (ED), and facilitation (what is needed to promote change) elements. Results/UNASSIGNED:A total of 31 individuals (mean [SD] age, 43.4 [11.0] years) participated in 6 focus groups. Twenty participants (64.5%) identified as male and most 13 (41.9%) as White; 17 (54.8%) reported being unemployed. Themes related to evidence included patients' experience of stigma and perceived minimization of their pain and medical problems by ED staff. Themes about context included the ED not being seen as a source of OUD treatment initiation and patient readiness to initiate treatment being multifaceted, time sensitive, and related to internal and external patient factors. Themes related to facilitation of improved care of patients with OUD seen in the ED included a need for on-demand treatment and ED staff training. Conclusions and Relevance/UNASSIGNED:In this qualitative study, patients with OUD reported feeling stigmatized and minimized when accessing care in the ED and identified several opportunities to improve care. The findings suggest that strategies to address stigma, acknowledge and treat pain, and provide ED staff training should be implemented to improve ED care for patients with OUD and enhance access to life-saving treatment.

Chronic pain is highly prevalent among patients with opioid use disorder (OUD). However, little is known about how pharmacological treatments for OUD, for example, extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX), affect pain. To begin addressing this question, we performed a secondary analysis of pain data on a large prospective 24-week, open-label, randomized-controlled comparative effectiveness trial of XR-NTX versus BUP-NX (X:BOT trial). Participants' pain status was measured by the EuroQol (EQ-5D). Based on their responses to the pain question at baseline, participants were dichotomized into "Pain" versus "No Pain" categories. Participant's pain status was evaluated every 4 weeks. A mixed effects longitudinal logistic regression model was fitted to examine the differential effect of XR-NTX versus BUP-NX on pain, modelling pain at all available follow-up assessments, adjusted for age, sex, and baseline pain. A total of 474 individuals who were successfully inducted onto their assigned medications were included in this analysis. Among participants endorsing pain at baseline, substantial reductions in pain were observed over the course of the study in both treatment groups. Howecver reduction in pain was slightly greater in the group treated with XR-NTX than the one treated with BUP-NX (OR = 1.60 [95% CI: 1.07-2.40], P = 0.023). Future research using instruments and design specifically focused on pain could extend the present observations and evaluate their clinical significance.

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.