(83) Long-Term Treatment Benefit of BUP-XR for Patients Struggling to Abstain from Opioids

Introduction
BUP-XR (SUBLOCADE®) is an extended-release monthly depot formulation of buprenorphine for the treatment of opioid use disorder (OUD). Treatment retention is key to abstinence and other aspects of successful treatment outcome. This integrated analysis of three phase 3 studies evaluated the additional benefit of BUP-XR long-term treatment beyond 6 months (up to 18 months) for OUD patients, especially those struggling to abstain from opioid use during the first 6 months of treatment.

Methods
Study 1 was a 24-week randomized, double-blind, placebo-controlled trial, where participants received 6 monthly injections of BUP-XR 300/100 mg (2X300 mg, then 4X100 mg, n=203), BUP-XR 300/300 mg (6X300mg, n=201) or placebo (n=100).1 Study 2 was a 49-week, open-label trial that enrolled 257 completers from Study 1 for 6 additional monthly injections and 412 de novo participants for 12 monthly injections.2 All participants in Study 2 received an initial injection of 300 mg with flexible subsequent doses of 100 mg or 300 mg based on investigator judgment. Study 3 was a 24-week, open-label extension study that enrolled 208 Study 2 completers for 6 additional flexible-dose monthly injections. Analysis included 787 participants with up to 18 months BUP-XR treatment (placebo participants were excluded). Percentage of abstinence was the percentage of each participant’s negative opioid UDS among his/her available UDS results. Early treatment response subgroups were defined based on participants’ percentage of abstinence for the first 6 months of ≤20% (early non-responders, n=178 [23%]), >20% to ≤50% (n=103 [13%]), and >50% (early responders, n=506 [64%]). Treatment emergent adverse events (TEAEs) were analyzed by 6-month treatment periods and subgroups.
For those treated beyond 6 months (n=490, 53%, 60%, 66% of the subgroups), the proportion of participants with negative opioid UDS by visit weeks was summarized by subgroups for the entire 18-month duration.

Results
Early non-responders showed a delayed response after the 6th injection; the proportion of participants with negative UDS was 16% at the end of month 6, but continuously improved to 73% by the end of 18 months. In the >20% to ≤50% subgroup, the proportion of participants with negative UDS showed durable improvement 2 weeks after the 4th injection (48%), and reached 85% at the end of 18 months. The proportion of early responders with negative UDS was 83% one week post the first injection and consistently reached 90% or above after the 3rd injection.
African Americans, injecting or daily opioid users were less likely to be early responders.
The incidence of TEAEs were lower in the second and third 6-month treatment periods for all subgroups. Early responders experienced more TEAEs than the early non-responders.

Conclusions
Extending treatment beyond 6 months provided additional improvement of opioid abstinence for patients with less favorable early treatment response, while the incidence of TEAEs decreased over time. The combined efficacy and safety profiles support clinical benefit for long-term treatment.

Trial Registration: ClinicalTrials.gov Identifier: NCT02357901 (Study 1), NCT02510014 (Study 2), NCT02896296 (Study 3)

References:
1. Haight, B.R. et al, 2019. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 393, 778-790.

2. Andorn, A.C. et al, 2020. Treating opioid use disorder with a monthly subcutaneous buprenorphine depot injection: 12-month safety, tolerability, and efficacy analysis. Journal of Clinical Psychopharmacology 40(3), 231-239.

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