Although buprenorphine (Subutex; Reckitt Benckiser) has been proven to be an effective treatment for opioid use disorder (OUD), it remains underused in the real-world setting. Authors of a study published in JAMA Network Open evaluated the feasibility (eg, acceptability, tolerability, and safety) of extended-release buprenorphine in patients who have untreated OUD who are experiencing minimal to mild withdrawal.
For this nonrandomized trial, data was gathered from 4 US urban teaching hospital emergency departments (EDs) that had experience initiating buprenorphine. The 635 patients enrolled were 18 years of age or older and were screened for opioid use. Patients were eligible if they were determined to have moderate to severe OUD with a urine point-of-care toxicology test that was positive for opioids, had a Clinical Opioid Withdrawal Scale (COWS) score that was less than 8 (representing minimal to mild withdrawal), and were English speakers.
All patients received a 24-mg dose of CAM2038, which is equivalent to 16 mg of buprenorphine, daily over a 7-day period. Patients remained in the ED for 4 hours following injection so they can be observed for worsening or precipitated withdrawal. Additionally, ancillary medications (eg, acetaminophen, ibuprofen, antiemetics) for specific symptoms were available per protocol, with patients being referred to community-based programs or clinicians for ongoing OUD treatment as usual for each site.
The primary outcomes for this study include the following: participants who experienced a 5-point or greater increase in COWS score within 4 hours of extended-release buprenorphine injection; transitioned to moderate or greater withdrawal (COWS scores of ≥13) within 4 hours of injection; or experienced precipitated withdrawal within 1 hour of injection. The investigators hypothesized that within 4 hours of injection: less than 20% of patients would experience a 5-point or greater increase in COWS scores; less than 10% would transition to moderate or greater withdrawal (COWS score of ≥13); and less than 10% would experience a precipitated withdrawal within 1 hour.
Of the total 635 patients enrolled, only 100 patients were eligible for the analysis and included in the results. The mean (SD) age was 36.5 (8.7) years, and of these patients, 28 were female. Most of the patients were White (51%) who reported unstable housing within the past 12 months (48%) with public insurance, such as Medicaid (79%).
In addition, 10 patients (95% CI, 4.9%-17.6%) experienced a 5-point or greater increase in COWS scores within 4 hours of the extended-release buprenorphine injection, and of these, 7 (95% CI, 2.9%-13.9%) transitioned to moderate or greater withdrawal and experienced precipitated withdrawal. Only 2 of the 7 patients (95% CI, 0.2%-7.0%) had developed precipitated withdrawal within 1 hour of the injection, the remaining within 4 hours. Further, the 7 patients who experienced precipitated withdrawal had also tested positive for fentanyl, as well as 70% of the total enrolled population; however, 63% using fentanyl underwent uneventful inductions.
Immediately after injection, the mean pain score was 2.9 (2.7) and the median was 2.0 (range: 1-10). At the 30-minute mark, the mean and median scores were 0.7 (1.2) and 0 (range: 0-5), respectively, and at 4 hours, the pain scores were 0.6 (1.7) and 0 (range: 0-10), respectively. Additionally, most patients did not experience erythema or swelling at 30 minutes (96% and 97%, respectively) and at 4 hours (98% and 98%, respectively).
At baseline, 6 patients had self-reported an overdose event in the 7 days prior to injection, and at 7 days after the injection, there were no reports of opioid overdose. Additionally, buprenorphine was present in 96% of the available 81 urine toxicology samples. A total of 43 samples were positive for any opioid (fentanyl only: 21; opiates and fentanyl: 11; methadone and fentanyl: 1; opiates: 7; oxycodone: 2; and methadone: 1), and there were other samples that tested for different drugs (methamphetamine: 22; cocaine: 25; phencyclidine: 4; benzodiazepines: 16; tetrahydrocannabinol: 35; and 3,4-methylenedioxymethamphetamine: 8).
Key Takeaways
- Feasibility and Safety of Extended-Release Buprenorphine: The study found that extended-release buprenorphine is feasible and generally safe for patients with opioid use disorder (OUD) who are experiencing minimal to mild withdrawal and had Clinical Opioid Withdrawal Scale (COWS) scores of 4 to 7. Less than 20% experienced a significant increase in withdrawal symptoms, and precipitated withdrawal was considered rare.
- Positive Patient Outcomes: Most patients reported a positive experience with extended-release buprenorphine, with 52% rating it as completely effective. Additionally, 73% continued with OUD treatment after the initial 7-day period, indicating good acceptance and adherence.
- Limitations and Future Research: The study's limitations include a small sample size, strict eligibility criteria, and a lack of control conditions. Future research is recommended to further assess the criteria and benefits for patients with COWS scores of 0 to 3.
Further, a total of 14 adverse events (AEs) were reported in 13 patients during the 7-day observation period, and included precipitated withdrawal (n = 7), nausea and vomiting (n = 1), transient loss of smell (n = 1), and substance use and depression (n = 1). Additionally, 5 of the 14 events were considered serious because hospitalization was required, of which 2 were medication-related. Among the 5 serious AEs, 2 were among the 7 patients who experienced precipitated withdrawal.
Of the 93 patients who completed the day 7 follow-up, 92 had responded to their overall experience with extended-release buprenorphine on a scale of 1 (completely ineffective) to 5 (completely effective), of which 48 patients (52%) rated a 5, 24 (26%) rated a 4, 12 (13%) rated a 3, 4 (4%) rating a 2, and 4 (4%) rating a 1. Approximately 73% of patients enrolled received OUD treatment on day 7 following enrollment, and the remaining 23% reported not needing further OUD treatment (20%) or were unable to be contacted (7%).
The investigators note that there are limitations to the study, including the small number of academic medical center EDs to collect data, the strict eligibility criteria reducing the sample size, and ready access to injectable medication. The investigators also acknowledge that there was no control condition, and that not including patients with COWS scores of 0 to 3 may be considered selection bias. Finally, the authors express that additional research to further assess the criteria use and the risk benefit analysis for use in patients with COWS scores of 0 to 3 can be beneficial.
References
D’Onofrio G, Herring AA, Perrone J, et al. Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal. JAMA Netw Open. 2024;7(7):e2420702. doi:10.1001/jamanetworkopen.2024.20702
