Lee JD, et al. - The intent of the authors was to compute the difference in opioid relapse-free survival between extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) for opioid relapse prevention. Initiating patients to XR-NTX was found to be difficult than BUP-NX. This exerted a negative impact on the overall relapse. Nonetheless, once initiated, both medications were equally safe and effective. In order to facilitate the induction to XR-NTX and for improving the treatment retention for both medications, advanced research was warranted.

Methods

• The design of this study was a 24 week, open-label, randomised controlled, comparative effectiveness trial.
• It was carried out at eight US community-based inpatient services, with follow-up of enrollees as outpatients.
• Candidates were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days.
• Patients were stratified by treatment site and opioid use severity to receive XR-NTX or BUP-NX.
• XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior).
• A web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) was used.
• The primary outcome included the opioid relapse-free survival during 24 weeks of outpatient treatment.
• Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use.

Results

• A total of 570 enrollees were randomly allocated to receive XR-NTX (n=283) or BUP-NX (n=287), between Jan 30, 2014, and May 25, 2016.
• The last follow-up visit was Jan 31, 2017. XR-NTX displayed a significant induction hurdle: Fewer enrollees successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p < 0.0001).
• Among individuals who were randomly assigned (intention-to-treat population, n=570), greater 24 week relapse events were discovered for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1.36, 95% CI 1.10-1.68).
• Most or all of this variation accounted for by early relapse in approximately all (70 [89%] of 79) XR-NTX induction failures.
• Amongst those who were successfully inducted (per-protocol population, n=474), similar 24 week relapse events were determined across study groups (p=0.44).
• Compared with XR-NTX, opioid-negative urine samples (p < 0.0001) and opioid-abstinent days (p < 0.0001) favoured BUP-NX among the intention-to-treat population.
• However, these were similar across study groups among the per-protocol cohort.
• Initially, the self-reported opioid craving was less with XR-NTX than with BUP-NX (p=0.0012), then converged by week 24 (p=0.20).
• No variation existed in the treatment-emergent adverse events including overdose between treatment groups, with the exception of mild-to-moderate XR-NTX injection site reactions.
• An occurrence of 5 fatal overdoses was reported (two in the XR-NTX group and three in the BUP-NX group).