Pain and treatment outcomes after initiating methadone vs buprenorphine among medicare patients with opioid use disorder and comorbid chronic pain: A target trial emulation

Background: Methadone and buprenorphine, effective treatments for opioid use disorder (OUD), also provide analgesia for managing pain, which is commonly experienced by patients with OUD. Limited population-based evidence exists comparing pain-related and treatment outcomes for methadone versus buprenorphine among patients with OUD and comorbid pain. The study aims to examine pain-related and treatment outcomes among Medicare patients with comorbid pain and OUD who initiated methadone or buprenorphine. Methods and findings: We conducted a retrospective cohort study with target trial emulation using the 100% Medicare data from 2020 to 2023. Participants included patients with comorbid chronic pain and OUD who initiated methadone or buprenorphine. The key dependent variables were pain-related outcomes that included hospitalization and emergency department (ED) visit due to pain, and treatment outcomes that included opioid overdose and all-cause mortality. Outcomes were assessed 1 year following treatment initiation. Intention-to-treat and per-protocol analyses were conducted to estimate incidence rate ratios (IRRs) for pain-related outcomes and opioid overdose and hazard ratios (HRs) for all-cause mortality. For each outcome, we also calculated the adjusted risk difference (aRD) between the methadone and buprenorphine groups. We identified 49,727 eligible Medicare patients (mean [SD] age, 59.0 [11.6] years; 24,538 [49.3%] female and 25,189 [50.7%] male). Of the identified patients, 16,174 (32.5%) initiated methadone solely administered at opioid treatment programs, and 33,553 (67.5%) initiated buprenorphine primarily prescribed at office-based clinics. Compared with buprenorphine, initiation of methadone was associated with lower adjusted incidence rates of pain-related hospitalization (IRR, 0.64 (95% CI [0.58, 0.70]; P