New Extended Release Buprenorphine (XR-BPN) research and where to next
Co-authors: Professor Michael Farrell, Dr Briony Larance and Marianne Byrne
Opioid dependence and injecting drug use account for the greatest burden attributable to illicit drug use in the world. In Australia, opioid deaths have increased by 50 per cent in the past decade; overdoses now account for more deaths than traffic accidents.
Methadone and buprenorphine are established as effective opioid agonist treatments (OAT) for opioid dependence, and classed as essential medicines for this indication by the World Health Organisation. Systematic reviews have demonstrated they are highly effective in reducing illicit opioid use, HIV and HCV incidence, criminal activity, overdose, and mortality. Despite this, global OAT coverage is low (16 per cent in 2017).
Australia’s emphasis on supervised daily dosing means many clients must travel significant distances each day, affecting capacity to engage in other activities including employment, increasing stigma, and deterring some from entering treatment. Access to OAT in rural/regional areas is difficult, given low prescriber numbers and lengthy distances. Many pay out-of-pocket dosing fees to pharmacies and private clinics, presenting another barrier to treatment. Daily dosing is a costly service model of delivering OAT, occupying considerable staff time, though daily clinical contact may assist some in structuring daily life.
Recently developed extended-release buprenorphine formulations (XR-BPN) could transform OAT. They are administered by subcutaneous injection, slowly releasing buprenorphine over the dosing interval, which can last a month. Only two randomised-controlled trials (RCT), have been published, both company-sponsored for registration purposes.
The XR-BPN RCTs findings
The first RCT, Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder, found the formulation used was superior to placebo in abstinence. Treatment with XR-BPN was also well tolerated.
The second RCT, Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder found XR-BPN was similar to sublingual buprenorphine in reducing illicit opioid use.
Two extended follow up studies have been reported: Long-term safety of a weekly and monthly subcutaneous buprenorphine depot (CAM2038) in the treatment of adult out-patients with opioid use disorder, and Effects of monthly buprenorphine extended-release injections on patient-centered outcomes: A long-term study. Whilst both found that XR-BPN delivered weekly or monthly was well tolerated with a systemic safety profile consistent with the known profile on sublingual buprenorphine, there was marked variation in observed treatment retention
The two randomised trials required weekly clinic attendance including urine drug screening, so they provide limited data on the benefits of XR-BPN as it would be delivered in usual practice. The last RCT monitored trial participants on weekly or monthly basis and had high retention rates. None of the studies reported have included a cost-effectiveness analysis.
Authors in each study included calls for further research into types of patients who may particularly benefit from such extended-release forms of buprenorphine.
Perceptions of XR-BPN
We’ve recently conducted a cross-sectional study to evaluate perceptions of XR-BPN for opioid use disorder among people who regularly use opioids in Australia, enrolling 402 participants from Sydney, Melbourne and Hobart. Here are some of the key findings:
- Two-thirds (68 per cent) believed the XR-BPN might be a good treatment option for them. Participants who believed XR‐BPN might be a good treatment option for them were more likely to be aged 26–35 years (versus > 55 years), female and had completed fewer years of education. They were also more likely to report past‐month heroin and methamphetamine use. Neither life‐time nor current OAT were associated with participants’ believing that XR‐BPN was a good treatment option for them.
- Monthly injections were preferred. 47 per cent of participants reported being ‘extremely likely’ to use a monthly buprenorphine injection. 27 per cent of participants reported being ‘extremely likely’ (10 on a 0–10 Likert scale) to use a weekly buprenorphine injection. Individual differences in Likert scale scores indicated that 54 per cent of participants reported no difference in their preference for monthly versus weekly injections.
- XR-BPN may be attractive to a wider group. Previous studies have indicated that prior experience with buprenorphine treatment is an important factor influencing perceptions of buprenorphine yet, in the current study, neither life‐time nor current methadone or buprenorphine ± naloxone use were associated with participants believing that XR‐buprenorphine was a good treatment option for them.
XR-BPN could overcome many of the barriers in current OAT models and aid scale-up of treatment coverage in Australia, including in rural and regional areas, and among emerging opioid-dependent groups (e.g. those dependent upon pharmaceutical opioids). An Australian randomised XR-BPN trial would add to the limited international evidence-base for the intervention and determine efficacy and suitability within the local opioid-dependent population. Independently collected data are therefore urgently needed on outcomes for different patient groups, acceptability and cost-effectiveness of XR-BPN in Australia.