Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trialResearch in context

• Published in: EClinicalMedicine 2023-12, Vol.66, p.102311
• Main Authors: John Marsden, Mike Kelleher, Eilish Gilvarry, Luke Mitcheson, Jatinder Bisla, Angela Cape, Fiona Cowden, Edward Day, Jonathan Dewhurst, Rachel Evans, Will Hardy, Andrea Hearn, Joanna Kelly, Natalie Lowry, Martin McCusker, Caroline Murphy, Robert Murray, Tracey Myton, Sophie Quarshie, Rob Vanderwaal, April Wareham, Dyfrig Hughes, Zoë Hoare
• Format: Article
• Language: English
• Subjects: Cost-effectiveness; Effectiveness; Extended-release buprenorphine; Opioid use disorder; Standard of care
• ISSN: 2589-5370

Background: Daily methadone maintenance or buprenorphine treatment is the standard-of-care (SoC) medication for opioid use disorder (OUD). Subcutaneously injected, extended-release buprenorphine (BUP-XR) may be more effective—but there has been no superiority evaluation. Methods: This pragmatic, parallel-group, open-label, multi-centre, effectiveness superiority randomised, controlled, phase 3 trial was conducted at five National Health Service community-based treatment clinics in England and Scotland. Participants (adults aged ≥ 18 years; all meeting DSM-5 diagnostic criteria for moderate or severe OUD at admission to their current maintenance treatment episode) were randomly assigned (1:1) to receive continued daily SoC (liquid methadone (usual dose range: 60–120 mg) or sublingual/transmucosal buprenorphine (usual dose range: 8–24 mg) for 24 weeks; or monthly BUP-XR (Sublocade;® two injections of 300 mg, then four maintenance injections of 100 mg or 300 mg, with maintenance dose selected by response and preference) for 24 weeks. In the intent-to-treat population (senior statistician blinded to blinded to treatment group allocation), and with a seven-day grace period after randomisation, the primary endpoint was the count of days abstinent from non-medical opioids between days 8–168 (i.e., weeks 2–24; range: 0–161 days). Safety was reported for the intention-to- treat population. Adopting a broad societal perspective inclusive of criminal justice, NHS and personal social service costs, a trial-based cost-utility analysis estimated the Incremental Cost-effectiveness Ratio (ICER) per quality-adjusted life year (QALY) of BUP-XR versus SoC at the National Institute for Health and Care Excellence threshold. The study was registered EudraCT (2018-004460-63) and ClinicalTrials.gov (NCT05164549), and is completed. Findings: Between Aug 9, 2019 and Nov 2, 2021, 314 participants were randomly allocated to receive SoC (n = 156) or BUP-XR (n = 158). Participants were abstinent from opioids for an adjusted mean of 104.37 days (standard error [SE] 9.89; range: 0–161 days) in the SoC group and an adjusted mean of 123.43 days (SE 4.76; range: 24–161 days) in the BUP-XR group (adjusted incident rate ratio [IRR] 1.18, 95% confidence interval [CI] 1.05–1.33; p-value 0.004). The incidence of any adverse event was higher in the BUP-XR group than the SoC group (128 [81.0%] of 158 participants versus 67 [42.9%] of 156 participants, respectively—most commonly rapidly-resolving (