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

## TL;DR

This study compares methadone and buprenorphine for treating opioid use disorder and chronic pain in Medicare patients, finding that methadone may reduce pain-related hospitalizations and ER visits without worsening other outcomes.

## Contribution

The study provides population-based evidence comparing methadone and buprenorphine for pain and treatment outcomes in Medicare patients with opioid use disorder and chronic pain.

## Key findings

- Methadone was associated with lower pain-related hospitalizations and ED visits compared to buprenorphine.
- No significant differences were found in opioid overdose or all-cause mortality between the two treatments.
- Results may reflect differences in patient populations and treatment settings, not fully captured in Medicare data.

## Abstract

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.

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 < .001); aRD, −7.2 (95% CI [−8.8 to −5.7]) per 1,000 person-years) and ED visit (IRR, 0.87 (95% CI [0.82, 0.92]; P < .001); aRD, −10.2 (95% CI [−14.4, −5.9]) per 1,000 person-years) in per-protocol analyses, with no difference in opioid overdose (IRR, 1.02 (95% CI [0.93,1.10]; P = .72); aRD, 0.33 (95% CI [−1.5, 2.1]) per 1,000 person-years) and all-cause mortality (HR, 1.06 (95% CI, [0.81–1.39]; P = .66); aRD, 1.1 (95% CI [−1.3, 1.0]) per 1,000 person-years) rates. Similar results were observed in intention-to-treat analyses. Main study limitations included unmeasured confounders and limited generalizability.

This population-based cohort study of Medicare patients with comorbid chronic pain and OUD found that methadone administered at opioid treatment programs is associated with reduced hospitalizations and ED visits for pain-related visits while offering treatment outcomes similar to buprenorphine primarily prescribed at office-based clinics. The favorable pain-related outcomes in patients with methadone should be interpreted with caution, as the finding may reflect differences in the underlying patient population, treatment dosing practices, pharmacological properties, and treatment practice settings, which cannot be measured in Medicare data and merit further investigations.

Methadone and buprenorphine, effective treatments for opioid use disorder (OUD), also provide analgesia for managing pain, which is commonly experienced by patients with OUD.

While studies have examined pain outcomes among patients prescribed medications for OUD, their quality of evidence is low, with small sample sizes, and they are mostly restricted to patients in inpatient or peri- and post-operative settings.

Limited studies have also compared treatment outcomes between Medicare patients prescribed different types of medications for OUD after Medicare’s expansion covering methadone in 2020.

The analysis assessed pain-related and treatment outcomes during the follow-up (up to 1 year) after the initiation of methadone or buprenorphine among 49,727 Medicare patients with OUD and comorbid chronic pain.

We found lower incidence rates for pain-related hospitalizations and pain-related emergency room visits, with no difference in opioid overdose and all-cause mortality rates within 1 year following initiation of methadone compared with buprenorphine.

Methadone administered at opioid treatment programs may reduce hospitalizations and emergency room visits for pain-related visits while offering treatment outcomes similar to buprenorphine, primarily prescribed at office-based clinics.

The favorable pain-related outcomes in patients with methadone versus buprenorphine should be interpreted with caution, as the finding may reflect differences in the underlying patient population, treatment dosing practices, pharmacological properties, and treatment practice settings, which cannot be measured in Medicare data and merit further investigations.

The study findings are only generalizable to Medicare patients with chronic pain and receipt of methadone or buprenorphine for OUD and are limited by not fully accounting for confounders, particularly those that cannot be measured in Medicare data.

In a retrospective cohort study with a target emulation trial design, Wei and colleagues investigate pain-related outcomes, measured as hospitalization and emergency department visits, after methadone or buprenorphine initiation in Medicare beneficiaries treated for opioid use disorder with comorbid chronic pain.