Extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) were equally effective in preventing opioid abuse relapse, according to a randomized open-label trial published in the Lancet. However, the burden associated with XR-NTX injections may prevent successful treatment initiation.
In this 24-week trial, participants with a history of opioid abuse were randomly assigned to receive monthly intramuscular injections of XR-NTX (n=283) or daily self-administered sublingual BUP-NX (n=287). Participants who had opioid use disorder and had taken a non-prescribed opioid within 30 days of enrollment were included in this trial.
The trial’s primary outcome was survival for the 24-week duration of outpatient treatment without opioid relapse. Relapse was defined as self-reported use of a non-study opioid for 7 consecutive days or the use of a non-study opioid for 4 consecutive weeks assessed with urine toxicology or by self-report.
A greater percentage of patients was able to successfully initiate BUP-NX vs XR-NTX (94% vs 72%, respectively; P <.0001), primarily due to the easier administration route of BUP-NX. Relapse events during the 24-week period were greater in patients randomly assigned to the XR-NTX vs patients in the BUP-NX group (65% vs 57%, respectively; hazard ratio, 1.36; 95% CI, 1.10-1.68). These findings are attributable to early relapses observed in 89% of participants who were unable to initiate XR-NTX.
In patients who successfully initiated treatment, the 24-week relapse events were as frequent in the two groups (P =.44). In the intention-to-treat population, participants randomly assigned to receive BUP-NX had a greater number of opioid-negative urine samples and opioid-abstinent days than patients who had received XR-NTX (P <.0001 for both).
No differences were observed in the per-protocol population. Fewer patients receiving XR-NTX vs BUP-NX reported “craving” opioids (P =.0012), but this difference was no longer present at 24 weeks (P =.20). In addition, no differences in treatment-emergent adverse events were observed. Overdose events occurred in 18 and 10 patients administered XR-NTX and BUP-NX, respectively.
According to the investigators, the varied induction protocols used in this study may have affected the success of XR-NTX initiation, thereby limiting the findings. Also, the lack of a placebo group and the open-label design may have introduced potential study bias.
”Patients, families, and providers now have data to help them make complex treatment decisions involving personal preferences, detoxification options and risks, and long-term outcomes,” concluded the investigators.
Lee JD, Nunes EV Jr, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial [published online November 14, 2017]. Lancet. doi:10.1016/S0140-6736(17)32812-X.