Author: Megan Brooks
Medscape
For adults with high-risk opioid use disorder (OUD), both 100-mg or 300-mg monthly maintenance injections of extended-release buprenorphine improved opioid abstinence, but the higher dose seemed to work better in heavy fentanyl users, results of a randomized controlled trial showed.
These results are “particularly relevant because individuals with OUD in North America are increasingly exposed to highly potent synthetic opioids, such as fentanyl, a driver of high levels of opioid overdose deaths,” wrote the researchers, led by Rajinder Shiwach, MD, with Adams Clinical Dallas in DeSoto, Texas.
The study was published online on December 17 in JAMA Network Open.
Fentanyl-Driven Crisis
The opioid epidemic remains a public health crisis complicated by an increase in the use of highly potent synthetic opioids, mainly fentanyl.
Fentanyl exposure reduces the likelihood of successful buprenorphine initiation and shortens retention in treatment, creating an urgent need for evidence-based dosing strategies to improve treatment outcomes.
Extended-release buprenorphine, approved in the US and Canada for moderate-to-severe OUD, improves abstinence and treatment retention compared with placebo, but optimal maintenance dosing in people who use fentanyl remains unclear.
To investigate, Shiwach and colleagues conducted a multicenter, randomized, double-blind trial at 28 outpatient treatment centers in the US and Canada, which included 435 adults (mean age, 42 years; 43% women) with moderate or severe OUD who injected opioids, used high doses of opioids, or used fentanyl.
Nearly three quarters of participants were using fentanyl at screening. Polysubstance use was common, and about one third reported a prior opioid overdose.
After completing buprenorphine induction and initiation of extended-release buprenorphine, participants were randomly assigned in a 1:1 ratio to receive eight additional monthly maintenance injections of either 100-mg or 300-mg of extended-release buprenorphine.
Rapid Reduction in Opioid Use
The proportion of responders (defined as weekly opioid abstinence of at least 80% for weeks 20-38, the primary outcome) was similar in the 100-mg and 300-mg groups (20.2% and 23.2%; difference, 2.6%; P = .48).
Both doses led to rapid and sustained reductions in opioid use, with the frequency of use falling from more than 43 instances at screening to fewer than three instances by week 3 (through week 38).
Measures of craving and withdrawal similarly declined early and remained low during maintenance treatment, and prespecified subgroup analyses showed no significant differences between groups.
However, dose differences emerged in post hoc subgroup analyses focused on fentanyl exposure.
Responder rates were significantly higher with the 300-mg maintenance dose among those who reported daily fentanyl use (24.3% vs 13.3%; difference, 11.1%), used fentanyl 14 or more times per week (20.2% vs 8.0%; difference, 12.2%), or both (22.2% vs 6.8%; difference, 15.4%).
Both maintenance doses were well tolerated with no new safety signals identified. Injection site reactions were more common with the higher dose but were generally mild-to-moderate and did not lead to treatment discontinuation.
“Taken together, these data add to the growing evidence for efficacy and safety of extended-release buprenorphine formulations for patients who use fentanyl,” investigators wrote.
Clinically Relevant…With Caveats
The findings “lend further support of the efficacy and safety of higher doses of extended-release injectable buprenorphine for persons with OUD who use fentanyl,” Sandra A. Springer, MD, with Yale School of Medicine in New Haven, Connecticut, wrote in a linked commentary.
However, Springer noted that all participants received two 300-mg injections during induction before randomization — a more rapid induction strategy, which may have led to higher retention and reduced opioid use and craving in all participants than are typically seen.
This rapid induction strategy is “not yet traditionally used in most standard outpatient clinic settings but should be considered as an option for persons who use fentanyl, given that rapid inductions are being found to be safe and effective,” Springer wrote.