Provider costs of treating opioid dependence with extended-release buprenorphine in Australia.

INTRODUCTION: The costs of providing medication-assisted treatment for opioid dependence can determine its scale of provision. To provide estimates of the costs of extended-release buprenorphine (BUP-XR), we performed a bottom-up costing analysis of provider operational treatment costs. METHODS: Data were collected in a single-arm open label trial of BUP-XR injections conducted in specialist public drug treatment services and primary care private practices in three Australian states (the CoLAB study). The unit costs of resources used for each activity were combined with quantities used at each participating facility to arrive at the average annual cost per client. RESULTS: One hundred participants across the six health facility sites received monthly subcutaneous BUP-XR injections administered by a health-care practitioner. The average cost of providing 1 year of treatment per participant was $6656 ($6026-$8326). Screening cost (initial assessment and medical history) was $282 while monthly follow-up appointments cost $531 per client. The main cost driver was the monthly treatment costs accounting for 79% of the average annual client cost, with medication costs comprising 95% of this cost. DISCUSSION AND CONCLUSION: With medication costs making up the largest proportion of treatment costs, treatment using BUP-XR has the potential to free up other health system resources, for example, staff time. The costs reported in this study can be used in an economic evaluation to estimate the net benefit or cost-effectiveness of BUP-XR especially when compared to other opioid agonist treatments.

Perceptions of extended-release buprenorphine among people who received medication for opioid use disorder in jail: a qualitative study.

BACKGROUND: Incarceration provides an opportunity for health interventions, including opioid use disorder (OUD) treatment and prevention of opioid-related overdoses post-release. All FDA-approved forms of medication for OUD (MOUD) treatment were mandated in several Massachusetts jails in 2019, with some jails offering extended-release buprenorphine (XR-Bup). Little is known about patient perspectives on and experiences with XR-Bup in carceral settings. METHODS: We conducted semi-structured interviews in 2022 with community-dwelling people who received MOUD during a recent incarceration in a Massachusetts jail. We asked participants about their experiences with and perspectives on XR-Bup while in jail. Qualitative data were double-coded deductively and reviewed inductively to identify emergent themes, which were structured using the Theoretical Framework of Acceptability (TFA). RESULTS: Participants (n = 38) had a mean age of 41.5 years, were 86% male, 84% White, 24% Hispanic, and 95% continued to receive MOUD at the time of their interview, including 11% receiving XR-Bup. Participants who viewed XR-Bup favorably appreciated avoiding the taste of sublingual buprenorphine; avoiding procedural difficulties and indignities associated with daily dosing in carceral settings (e.g., mouth checks, stigmatizing treatment from correctional staff); avoiding daily reminders of their addiction; experiencing less withdrawal; having extra time for other activities, such as work; and reduction of diversion of MOUD within the jail setting. Participants who viewed XR-Bup less favorably preferred to maintain their daily dosing routine; liked daily time out of their housing unit; wanted to know what was "going into my body everyday"; and feared needles and adverse events. Participants also reported that jail clinicians used XR-Bup for patients who were previously caught diverting sublingual buprenorphine, suggesting limited patient participation in decision-making around XR-Bup initiation in some jails. CONCLUSION: People who received MOUD in Massachusetts jails had both favorable and unfavorable views and experiences with XR-Bup. Understanding these preferences can inform protocols in jails that are considering implementation of XR-Bup treatment.

Prescribing of extended release buprenorphine injection for Medicaid beneficiaries, 2018-2022.

BACKGROUND AND AIMS: Extended release buprenorphine injection (INJ-BUP) has been available in the United States since 2018. INJ-BUP has the potential to positively impact opioid use disorder (OUD) treatment outcomes by providing additional treatment options . As one of the largest payers of OUD treatment in the US, Medicaid coverage is important for access and uptake of INJ-BUP. Uptake of INJ-BUP among Medicaid beneficiaries has not been described since 2019 and variation in uptake by state has not previously been explored. We aimed to measure prescribing of INJ-BUP for Medicaid beneficiaries since 2018, nationwide and by state. METHODS: We analyzed State Drug Utilization Data from 2017 to 2022 and calculated the number of prescription fills for INJ-BUP and oral buprenorphine paid by Medicaid. To compare across states, we calculated the number of prescription fills per 100 Medicaid beneficiaries treated for OUD using data from Transformed Medicaid Statistical Information System Substance Use Disorder (T-MSIS SUD) Data Books. Data sources are publicly available. RESULTS: The number of prescription fills for INJ-BUP paid by Medicaid increased from 4322 (0.1% of all buprenorphine prescription fills) in 2018 to 186 861 (2.0%) in 2022. Each year the increase in fills exceeded the prior year change, indicating accelerating uptake. There was notable variability across states. CONCLUSIONS: The number of extended release buprenorphine injection prescriptions among US Medicaid beneficiaries treated for opioid use disorder increased from over 4000 prescriptions in 2018 to over 185 000 in 2022 but uptake is much less than observed in other countries over shorter time periods.

Successful administration of extended-release buprenorphine in the emergency department.

INTRODUCTION: The ongoing opioid epidemic in the United States has resulted in a substantial increase in overdose deaths and related morbidity and mortality. Given that emergency departments (ED) frequently serve as the initial point of contact for individuals experiencing opioid overdose or seeking treatment for opioid use disorder (OUD), ED clinicians have a pivotal role to play in providing prompt and effective treatment for OUD. While ED clinicians routinely administer sublingual and other transmucosal formulations of buprenorphine, extended-release buprenorphine (BUP-XR) remains underutilized in the ED. CASE REPORT: We present a case involving the successful administration of BUP-XR in the ED to a patient experiencing spontaneous opioid withdrawal. The patient tolerated test dosing of sublingual buprenorphine (BUP-SL) and subsequently received BUP-XR in the ED. Following this intervention, the patient was referred to the hospital-affiliated substance use disorder outpatient clinic, where he has since demonstrated successful follow-up and retention in treatment. CONCLUSION: Our report adds to the existing limited literature on the administration of BUP-XR in the ED and highlights the need for more comprehensive clinician teaching and guidance, as well as the establishment of in-hospital protocols for BUP-XR. Despite these challenges, our case indicates that initiating BUP-XR could be a viable and effective option for ED patients with OUD.

Community buprenorphine continuation post-release following extended release vs. sublingual buprenorphine during incarceration: a pilot project in Maine.

BACKGROUND: The aim of our study was to evaluate the post-release outcomes of incarcerated individuals with opioid use disorder (OUD) treated with extended-release buprenorphine (XRB) in a rural county jail. Administrative data were collected from a pilot program within a jail in Maine that introduced XRB treatment in 2022 and a comparable jail utilizing sublingual buprenorphine (SLB) during the same period to compare post-release outcomes. Log-binomial regression models were used to estimate the risk ratio (RR) and 95% confidence interval (CI) for jail use of XRB vs. SLB on post-release community buprenorphine continuation. RESULTS: From September 2022 to September 2023, 70 individuals who received XRB were released from the pilot jail and 130 individuals who received SLB were released from the comparison jail. After adjusting for age, sex, and buprenorphine use at entry to jail, individuals released from the pilot jail were almost 3 times (adjusted RR = 2.67, 95% CI 1.84, 3.88) as likely to continue community buprenorphine treatment post-release relative to the comparison jail. In addition, utilization of XRB allowed for expanded access to OUD treatment, was well tolerated, and reduced medication diversion. CONCLUSIONS: In this pilot program in Maine, XRB treatment during incarceration was associated with higher post-release community buprenorphine continuation when compared to individuals treated with SLB. These findings provide strong evidence for the superiority of XRB vs. SLB for the treatment of OUD in jail settings.

Extended-release versus oral buprenorphine as opioid maintenance treatment during pregnancy-maternal and neonatal outcomes.

OBJECTIVE: To get information on subcutaneous extended-release buprenorphine as opioid maintenance treatment during pregnancy, we compared it to orally administered buprenorphine and buprenorphine-naloxone treatments. We hypothesized that maternal and neonatal outcomes do not differ between the treatment groups. Study design In this population-based cohort study, 60 pregnant individuals receiving non-changed opioid maintenance treatment for opioid use disorder with a buprenorphine product from the time before conception to the time after delivery and their newborns were included. They were divided into three groups based on the pharmacotherapy with subcutaneous extended-release buprenorphine, sublingual buprenorphine, or buprenorphine-naloxone. Statistical analyses were conducted using Fischer's exact tests, ANOVA tests, and Kruskal-Wallis tests. All the statistical tests were two-tailed. RESULTS: The frequency of pregnancy or delivery complications did not significantly differ between the group receiving extended-release buprenorphine and the other groups. During pregnancy, 38 % of the women used illicit drugs concomitantly, with equal frequency in the extended-release buprenorphine group and the other groups. Of the neonates, 93 % were born full-term and 90 % got at least eight Apgar points in one minute age, without significant differences between the groups (p = 0.57). The need for pharmacotherapy for neonatal opioid withdrawal syndrome was the lowest in the extended-release buprenorphine group (25 %) and highest in the sublingual buprenorphine group (67 %). Still, the difference between the treatment groups did not reach statistical significance (p = 0.17). Among all neonates, the breastfed infants were less likely to receive pharmacotherapy for withdrawal symptoms than the formula-fed ones (p = 0.048). CONCLUSIONS: Extended-release buprenorphine with steady drug concentration seems to be a promising pharmacotherapy option during pregnancy for mothers. Maternal health during pregnancy may contribute to the well-being of newborns. Larger trials are urgently needed to confirm these results..

96-week retention in treatment with extended-release subcutaneous buprenorphine depot injections among people with opioid dependence: Extended follow-up after a single-arm trial.

BACKGROUND: The most recent formulation of buprenorphine treatment is extended-release depot injections (BUP-XR) that are administered subcutaneously by health care professionals. This study aimed to observe treatment outcomes of BUP-XR delivered in standard practice during a 96-week follow-up period in a community setting. METHODS: This study is an extension of the CoLAB study, a prospective single-arm, multicentre, open label trial (N=100, 7 sites in Australia) among people with opioid dependence who received monthly injections of BUP-XR to evaluate the retention in treatment. Participants were followed for 96 weeks, comprising 48 weeks of the CoLAB study followed by a 48-week extension. RESULTS: Of 100 participants at baseline, 47 were retained on BUP-XR at 96 weeks. The median time retained on monthly depot was 90 weeks. Heroin use (adjusted OR=0.19, P=0.012) in the month prior to baseline was associated with lower odds of retention on BUP-XR. Older age at first opioid use (adjusted OR= 1.08, P=0.009) and longer duration in OAT at baseline (adjusted OR= 1.12, P=0.001) were associated with increased retention. Prevalence of past four-weeks opioid use was estimated at 4% at 96 weeks of treatment (prevalence 0.04, 95%CI: 0.00-0.11) compared to 15% at baseline. Quality of life and medication treatment satisfaction improved over time for those retained in treatment. CONCLUSION: This is one of the few studies to describe long term (96 week) retention in treatment with BUP-XR in a community setting. It displayed retention rates with 47% of participants completing 96 weeks of treatment with BUP-XR. Patient reported outcomes suggest improvements in client wellbeing. FUNDING: Indivior.

Tinkering with care: Implementing extended-release buprenorphine depot treatment for opioid dependence.

We examine how extended-release buprenorphine depot (BUP-XR) is put to use and made to work in implementation practices, attending to how care practices are challenged and adapted as a long-acting technology is introduced into service in opioid agonist treatment (OAT) in Australia. Our approach is informed by ideas in science and technology studies (STS) emphasising the irreducible entanglement of care practices and technology, and in particular the concept of 'tinkering' as a practice of adaptation. To make our analysis, we draw on qualitative interview accounts (n = 19) of service providers involved in BUP-XR implementation across five sites. Our analysis considers the disruptive novelty of BUP-XR. Tinkering to make a novel technology work in practice slows down the expectation of implementation in relation to transformative innovation, despite the promise of dramatic or rapid change. Tinkering allowed for more open relations, for new care practices that departed from the routine and familiar, opening potential for how BUP-XR could be put to use and made to work in its new situation, and as its situation evolved along-with its implementation. Flexibility and openness of altering relations was, however, at times, held in tension with inflexibility and closure. This analysis identifies a concern for what is made present and what is made absent in the altered care network affected by BUP-XR, with the multiple effects of supervised daily dosing practices thrown into relief as they become absented. Tinkering to implement BUP-XR locally connects with a broader assemblage of trial and movement in the constitution of treatment. The introduction of long-acting technologies prompts new questions about embedded implementation practices, including supervised dosing, urinalysis, the time and place of psychosocial support, and how other social aspects of care might be recalibrated in drug treatment.

Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial.

Background: Daily methadone maintenance or buprenorphine treatment is the standard-of-care (SoC) medication for opioid use disorder (OUD). Subcutaneously injected, extended-release buprenorphine (BUP-XR) may be more effective-but there has been no superiority evaluation. Methods: This pragmatic, parallel-group, open-label, multi-centre, effectiveness superiority randomised, controlled, phase 3 trial was conducted at five National Health Service community-based treatment clinics in England and Scotland. Participants (adults aged ≥ 18 years; all meeting DSM-5 diagnostic criteria for moderate or severe OUD at admission to their current maintenance treatment episode) were randomly assigned (1:1) to receive continued daily SoC (liquid methadone (usual dose range: 60-120 mg) or sublingual/transmucosal buprenorphine (usual dose range: 8-24 mg) for 24 weeks; or monthly BUP-XR (Sublocade;® two injections of 300 mg, then four maintenance injections of 100 mg or 300 mg, with maintenance dose selected by response and preference) for 24 weeks. In the intent-to-treat population (senior statistician blinded to blinded to treatment group allocation), and with a seven-day grace period after randomisation, the primary endpoint was the count of days abstinent from non-medical opioids between days 8-168 (i.e., weeks 2-24; range: 0-161 days). Safety was reported for the intention-to- treat population. Adopting a broad societal perspective inclusive of criminal justice, NHS and personal social service costs, a trial-based cost-utility analysis estimated the Incremental Cost-effectiveness Ratio (ICER) per quality-adjusted life year (QALY) of BUP-XR versus SoC at the National Institute for Health and Care Excellence threshold. The study was registered EudraCT (2018-004460-63) and ClinicalTrials.gov (NCT05164549), and is completed. Findings: Between Aug 9, 2019 and Nov 2, 2021, 314 participants were randomly allocated to receive SoC (n = 156) or BUP-XR (n = 158). Participants were abstinent from opioids for an adjusted mean of 104.37 days (standard error [SE] 9.89; range: 0-161 days) in the SoC group and an adjusted mean of 123.43 days (SE 4.76; range: 24-161 days) in the BUP-XR group (adjusted incident rate ratio [IRR] 1.18, 95% confidence interval [CI] 1.05-1.33; p-value 0.004). The incidence of any adverse event was higher in the BUP-XR group than the SoC group (128 [81.0%] of 158 participants versus 67 [42.9%] of 156 participants, respectively-most commonly rapidly-resolving (mild-moderate range) pain from drug administration in the BUP-XR group (121 [26.9%] of 450 adverse events). There were 11 serious adverse events (7.0%) in the 158 participants in the BUP-XR group, and 18 serious adverse events (11.5%) in the 156 participants in the SoC group-none judged to be related to study treatment. The BUP-XR treatment group had a mean incremental cost of £1033 (95% central range [CR] -1189 to 3225) and was associated with a mean incremental QALY of 0.02 (95% CR 0.00-0.05), and an ICER of £47,540 (0.37 probability of being cost-effective at the £30,000/QALY gained willingness-to-pay threshold). However, BUP-XR dominated the SoC among participants who were rated more severe at study baseline, and among participants in maintenance treatment for more that 28 days at study enrolment. Interpretation: Evaluated against the daily oral SoC, monthly BUP-XR is clinically superior, delivering greater abstinence from opioids, and with a comparable safety profile. BUP-XR was not cost-effective in a base case cost-utility analysis using the societal perspective, but it was more effective and less costly (dominant) among participants with more severe OUD, or those whose current treatment episode was longer than 28 days. Further trials are needed to evaluate if BUP-XR is associated with better clinical and health economic outcomes over the longer term. Funding: Indivior.

18-Month efficacy and safety analysis of monthly subcutaneous buprenorphine injection for opioid use disorder: Integrated analysis of phase 3 studies.

BACKGROUND: Few studies investigate the natural history of patients on long-term treatment for opioid use disorder (OUD). We evaluated the long-term efficacy, safety, and tolerability experience of monthly extended-release buprenorphine (BUP-XR) in participants seeking treatment for OUD, via integrated analysis of phase 3 studies. METHODS: Study 1 was a 24-week randomized, double-blind, placebo-controlled trial of participants receiving monthly injections of BUP-XR (300 mg × 2, 100 mg × 4 [n = 203] or 300 mg × 6 [n = 201]) or placebo (n = 100). Study 2 was a 48-week, open-label trial enrolling 257 participants who completed study 1 and 412 de novo participants, to receive 6 and 12 BUP-XR injections, respectively. Study 3 was a 24-week, open-label extension enrolling 208 participants who completed study 2 for 6 additional injections. We assessed opioid abstinence as the proportion of urine opioid negative participants by visit and the percentage of each participant's negative opioid assessments during the first 6 months. RESULTS: In total, 916 participants were treated with BUP-XR or placebo. By the end of 18 months, 92.7 % of the de novo cohort and 81.8 % of the study 1 cohort were urine negative for opioids. Among early nonresponders (percentage of abstinence ≤20 %), 73.1 % were urine negative after 18 months. The longer treatment period was well tolerated, with no new safety concerns, and a low incidence of opioid withdrawal signs and symptoms, and hepatic disorder. CONCLUSIONS: Extending BUP-XR treatment beyond 6 months sustained improvement in opioid abstinence and was well tolerated, supporting clinical benefit up to 18 months. TRIAL REGISTRATION: NCT02357901 (study 1); NCT02510014 (study 2); NCT02896296 (study 3).

The switching process from buprenorphine sublingual tablets to the monthly buprenorphine subcutaneous depot injection in opioid dependent patients.

The 2018 European Union (EU) approved weekly and monthly subcutaneous buprenorphine depot injection (BUP-XR), for opioid substitution medication proved to offer some specific treatment benefits. The present study examines the process of switching from buprenorphine sublingual tablets (BUP-SL) to BUP-XR from a patient's point of view. In total, nine patients were surveyed by means of an open-answer questionnaire regarding course and side effects of the medication switch. Six of these patients were surveyed in more detail under BUP-SL, as well as 4 and 16 weeks after the switch to BUP-XR by means of a test battery of questions on socio-demography, withdrawal symptoms, craving, physical well-being, treatment satisfaction and concomitant use of illegal substances. Patients reported significant worse physical well-being and lower treatment satisfaction in 4 weeks compared with 16 weeks after the medication switch to the BUP-XR. Furthermore, they reported significant more frequent co-use of illicit drugs, worse physical well-being, lower treatment satisfaction and more craving experience 4 weeks after the switch compared with the treatment under BUP-SL. Patients 16 weeks under BUP-XR reported significant more illicit co-use and lower treatment satisfaction compared with patients under BUP-SL. Connections between therapy dissatisfaction, physical discomfort, experienced craving and drug co-consumption were discovered. In the first weeks after the medication switch, patients experience potentially distressing symptoms, which, however, seem to diminish over time. Close supervision and comprehensive patient education on possible burdens of the medication switch to the BUP-XR might prevent unfavourable treatment courses and premature therapy dropouts.

Rapid induction onto extended-release injectable buprenorphine following opioid overdose: A case series.

Background: Buprenorphine treatment has been associated with reduced non-prescribed opioid use and opioid related overdose (OD). We evaluated initial outcomes of rapid induction onto extended-release injectable buprenorphine (BUP-XR) within 7 days of emergency department presentation for unintentional OD. Methods: Between February 2019-February 2021, N = 19 patients with opioid use disorder received buprenorphine/naloxone (4/1 mg), followed by BUP-XR (300 mg) at induction and continued BUP-XR outpatient for 6 months. Primary outcomes included adverse events, repeat OD, and death. Results: For patients who received at least one dose of BUP-XR, there were no treatment related serious adverse events or symptoms of precipitated withdrawal. In addition, there were no repeat visits for ODs or deaths within 6 months of the initial OD. Discussion: These preliminary findings support the need for larger controlled clinical trials to examine the safety and efficacy of rapid induction of BUP-XR in patients with opioid use disorder at high risk of opioid OD. Rapid induction onto long-lasting injectable buprenorphine may be a promising and protective treatment approach in the future.

What to Expect With Pregnant or Postpartum Prescribing of Extended-Release Buprenorphine (CAM2038).

Weekly and monthly CAM2038 (Brixadi®) extended-release subcutaneous buprenorphine (XR bup) has been available in Europe and Australia for several years and was approved by the Food and Drug Administration in May 2023. Little is known about the clinical experience of patients and providers using this new medication during prenatal care. Two cases of pregnant persons with opioid use disorder receiving weekly XR bup in an ongoing randomized multi-site outpatient clinical trial are presented along with a brief review of the pharmacology and literature on XR bup formulations. The cases in pregnancy illustrate how treatment with the weekly formulation is initiated including how to make dose adjustments, which may be necessary given the longer half-life; it takes 1 month to achieve steady state. Injection site pain with medication administration was time limited and managed readily. Other injection site reactions experienced included subcutaneous erythema and induration that was delayed in onset and typically mild, resolving with minimal intervention. Delivery management and breastfeeding recommendations while on weekly XR bup were not different compared to sublingual buprenorphine (SL bup). Weekly XR bup is a new treatment for opioid use disorder that may be used in the obstetric population. Obstetric and addiction medicine clinicians should be aware of this new formulation as its use is expected to increase.

Buprenorphine exposure levels to optimize treatment outcomes in opioid use disorder.

The severity of the ongoing opioid crisis, recently exacerbated by the COVID-19 pandemic, emphasizes the importance for individuals suffering from opioid use disorder (OUD) to have access to and receive efficacious, evidence-based treatments. Optimal treatment of OUD should aim at blocking the effects of illicit opioids while controlling opioid craving and withdrawal to facilitate abstinence from opioid use and promote recovery. The present work analyses the relationship between buprenorphine plasma exposure and clinical efficacy in participants with moderate to severe OUD using data from two clinical studies (39 and 504 participants). Leveraging data from placebo-controlled measures assessing opioid blockade, craving, withdrawal and abstinence, we found that buprenorphine plasma concentrations sustained at 2-3 ng/ml (corresponding to ≥70% brain mu-opioid receptor occupancy) optimized treatment outcomes in the majority of participants, while some individuals (e.g., injecting opioid users) needed higher concentrations. Our work also included non-linear mixed effects modeling and survival analysis, which identified a number of demographic, genetic and social factors modulating treatment response and retention. Altogether, these findings provide key information on buprenorphine plasma levels that optimize clinical outcomes and increase the likelihood of individual treatment success. NLM identifiers: NCT02044094, NCT02357901.

Extended-release pharmacotherapy for opioid use disorder (EXPO): protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone.

BACKGROUND: Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness - monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated. METHODS: This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2-24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. DISCUSSION: This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere. TRIAL REGISTRATION: EU Clinical Trials register 2018-004460-63.

Can a new formulation of opiate agonist treatment alter stigma?: Place, time and things in the experience of extended-release buprenorphine depot.

INTRODUCTION: Stigma has corrosive effects on all aspects of care and can undermine individual and population health outcomes. Addiction-related stigma has implications for opiate agonist treatment (OAT) and the people who receive, provide and fund it. It is important to understand how stigma is made in OAT and the political purposes that it serves, in order to change the relations of stigma and avoid the reproduction of stigma in the delivery of new treatment formulations, such as extended release buprenorphine (BUP-XR). METHODS: Semi-structured qualitative interviews were conducted at two time points with participants in a prospective single-arm, multicentre, open-label trial of monthly BUP-XR. Thirty-six participants (25 men, 11 women) were interviewed, and of these 32 participated in a second interview to explore their experience of transition from other treatment to BUP-XR. RESULTS: Participants were highly aware of the of the social and material effects of stigma through the negative stereotypes attached to OAT and those who receive it. Participants narrated examples of how stigma governed as a biopower in the relations and practices of OAT provision at numerous levels: structural (such as in public discourse about OAT and the people who receive it, in media, in perceptions about the decisions of investment in medical technologies); organisational (policies about legitimate access to OAT); interpersonal (with health workers) and individual (self-identities). BUP-XR allowed greater freedom and normalcy for clients. The experience of BUP-XR drew attention to the stigmatising potential of time, place and things associated with other OAT requiring daily (or frequent) dosing, accentuating how stigma comes to be materialised as a relational effect of everyday practices. CONCLUSIONS: Receiving BUP-XR allowed participants to avoid some of the everyday biopolitical powers of other forms of OAT and to reshape self-identities. The altering of relations between time, place and things associated with other forms of OAT allowed participants to feel as though they "pass as normal" . However, the negative public discourse and stigma of OAT is a potential threat to BUP-XR to realise its potential for individual and population benefits.

Real-world outcomes with extended-release buprenorphine (XR-BUP) in a low threshold bridge clinic: A retrospective case series.

BACKGROUND: In clinical trial settings, extended-release buprenorphine (XR-BUP) is noninferior to sublingual buprenorphine and may offer some advantages. However, real-world experiences of XR-BUP are limited and outcomes are unknown for low-threshold clinics with high-risk populations. Practical guidance is lacking on overcoming treatment challenges, such as inability for some to stabilize on sublingual (SL) BUP for seven days prior to XR-BUP and ongoing craving/withdrawal symptoms during treatment. METHODS: Retrospective case series of a convenience sample of 40 serial adults with opioid use disorder (OUD) treated with XR-BUP from Massachusetts General Hospital bridge clinic from February 1, 2019, to July 31, 2019. RESULTS: Patients were mostly male (67.5%), non-Hispanic white (97.5%), unstably housed (77.5%), and average age of 32.1 years old. The average SL BUP dose prior to XR-BUP was 18.6 mg (standard deviation [SD] = 5; range 8-32) for an average treatment duration of 105 days (SD = 191; range 1-810). Ten (25%) patients received SL BUP for fewer than the seven recommended days (mean = 3.7, SD = 1.4, range = 1-6). Standard induction dosing was administered to 30%, empiric high-dose XR-BUP (300 mg monthly) was administered to 25%, and 55% were treated with supplemental SL BUP ranging from 4 to24mg, daily or as needed, for varying time periods. At the end of data collection, 65% remained on XR-BUP, 30% discontinued XR-BUP, and one patient was lost to follow-up. Acute care utilization rates were similar between patients who continued XR-BUP versus discontinued at 18.5% and 16.6%, respectively (χ2 = 0.02, p-value = 0.89). Toxicology was negative for other opioids in 65% of patients throughout treatment. There were no reports of overdose, withdrawal after use of opioids, or precipitated withdrawal after subsequent XR-BUP. Patients' most cited reason for discontinuing XR-BUP was a preference for SL BUP. CONCLUSION: This real-world evaluation of XR-BUP in a low-threshold clinic found that treatment was feasible, well tolerated, and outcomes were good, with most individuals choosing to continue treatment and a majority with no evidence of ongoing opioid use or precipitated withdrawal.

Characterizing initiation, use, and discontinuation of extended-release buprenorphine in a nationally representative United States commercially insured cohort.

BACKGROUND AND AIMS: While the United States is in the midst of an overdose epidemic, effective treatments are underutilized and commonly discontinued. Innovations in medication delivery, including an extended-release formulations, have the potential to improve treatment access and reduce discontinuation. We sought to assess extended-release buprenorphine discontinuation among individuals with opioid use disorder (OUD) in a real-world, nationally representative cohort. SETTING: United States PARTICIPANTS: Commercially insured individuals initiating one of four FDA-approved medications for opioid use disorder (MOUD) in 2018: extended-release buprenorphine, extended-release naltrexone, mucosal buprenorphine (mono- or co-formulated with naloxone), or methadone. MEASUREMENTS: Our primary outcome was medication discontinuation, defined as a gap of more than 14 days between the end of one prescription or administration and the subsequent dose. FINDINGS: We identified 14,358 individuals initiating MOUD in 2018, including 204 (1%) extended-release buprenorphine, 1,173 (8%) extended-release naltrexone, 12,171 (85%) mucosal buprenorphine, and 810 (6%) methadone initiations. Three months after initiation, 50% (95% confidence interval [CI] 40%-60%) of extended-release buprenorphine, 64% (95% CI 61%-69%) of extended-release naltrexone, 34% (95% CI 33%-35%) of mucosal buprenorphine, and 58% (95% CI 54%-62%) of methadone initiators had discontinued treatment. CONCLUSIONS: Across all treatment groups, medication discontinuation was high, and in this sample of early adopters with limited follow-up time, we found no evidence that extended-release buprenorphine offered a retention advantage compared to other MOUD in real-world settings. Retention continues to represent a major obstacle to treatment effectiveness, and interventions are needed to address this challenge even as new MOUD formulations become available.