Supplementary materials: Effectiveness and safety of therapies for patients with opioid use disorder: a systematic review and network meta-analysis

These are peer-reviewed supplementary materials for the article 'Effectiveness and safety of therapies for patients with opioid use disorder: a systematic review and network meta-analysis' published in the Journal of Comparative Effectiveness Research.S1: Search strategyS2: Inclusion and exclusion criteriaS3: Included studiesS4: Study characteristicsS5: Risk of bias assessmentS6: Statistical methodology details for the surrogate endpoint meta-analysis and matching treatment armS7: Surrogate meta-analysis resultsS8: Additional NMA results for efficacy outcomes based on different evidence sourceS9: NMA results for treatment discontinuation and illicit opioid useS10: Subgroup analyses resultsS11: NMA results for safety and HRQoL outcomesS12: PRISMA ChecklistAim: Opioid use disorder (OUD) leads to significant morbidity and mortality. While opioid agonist therapies like transmucosal buprenorphine and methadone are effective, they face challenges such as poor adherence, diversion risk and suboptimal abstinence rates, prompting the development of long-acting injectable (LAI) buprenorphine. However, comparative evidence among LAIs and versus standard treatments remains limited. The aim of this study is to provide comparative evidence among buprenorphine LAIs and versus oral opioid agonist treatments. Materials & methods: We conducted a systematic literature review and network meta-analysis (NMA) evaluating the effectiveness and safety of LAI buprenorphine treatments (extended-release buprenorphine [BUP-XR; monthly injection] and other BUP-LAI [weekly and monthly injection]) versus transmucosal buprenorphine, methadone and buprenorphine implants in adults with OUD. The review included randomized controlled trials (RCTs) and non-RCTs for LAIs (January 2012 and March 2025). Primary outcomes were treatment discontinuation and illicit opioid use. Secondary outcomes were safety and health-related quality of life. Data were synthesized using univariate NMAs, bivariate NMA with surrogate end point modelling. Studies with limited data and single-arm designs were incorporated by using study-level matching techniques. Results: Ninety-eight studies met the inclusion criteria. BUP-XR demonstrated the highest probability of achieving treatment retention and opioid abstinence across analyses. In combined evidence (RCTs and non-RCTs), BUP-XR showed significantly lower risk of illicit opioid use versus transmucosal buprenorphine (rate ratio [RR] 1.99; 95% credible interval [CrI]: 1.29–3.11) andmethadone (RR: 2.66; 95% CrI: 1.40–3.56). BUP-XR showed borderline significantly lower risk of illicit opioid use versus other BUP-LAI (RR: 1.81; 95% CrI: 0.97–3.55) and buprenorphine implant (RR: 2.28; 95% CrI: 0.98–5.38). Treatment discontinuation rates were similar between OUD treatments. Safety outcomes were generally comparable across treatments. Health-related quality of life indicated better recovery among patients treated with BUP-XR. Conclusion: BUP-XR may enhance treatment retention and abstinence over other OUD therapies, supporting its integration into clinical pathways. The results may help guide future updates to OUD treatment guidelines and policies aimed at optimizing the use of long-acting formulations. Additional research is needed to better define the comparative effectiveness of LAIs.