Pain and Treatment Outcomes After Initiating Methadone Versus Buprenorphine in Medicare Patients

26 Mar 20265 min read0 viewsJournal Feed

GIST

by Yu-Jung Jenny Wei, Almut G. Winterstein, Roger B.

Fillingim, Stephan Schmidt, Siegfried Schmidt 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.

Clinical Editorial

Context and study aim

The study investigates pain-related and treatment outcomes among Medicare beneficiaries with coexisting chronic pain and opioid use disorder (OUD) who initiated methadone versus buprenorphine.
The investigation employed a retrospective cohort design with target trial emulation to mirror a randomized trial within observational Medicare data from 2020–2023.

Design, population, and exposure

Data source encompassed the entirety of Medicare claims for the study period.
Participants included adults with documented chronic pain and OUD who began methadone or buprenorphine treatment.
Initiation pathways differed by setting: methadone was primarily initiated in opioid treatment programs; buprenorphine initiation was largely at office-based clinics.
Analyses included both intention-to-treat and per-protocol approaches to approximate treatment effects.

Outcomes assessed

Pain-related outcomes: hospitalizations and emergency department visits attributable to pain.
Treatment outcomes: opioid overdose events and all-cause mortality.
Follow-up for outcomes extended to 12 months after treatment initiation.
For each outcome, estimates included incidence rate ratios (IRRs) and hazard ratios (HRs), with adjusted risk differences (aRDs) presented to quantify absolute risk differences between the methadone and buprenorphine groups.

Key findings on pain-related morbidity

Initiation of methadone was associated with lower adjusted incidence rates of pain-related hospitalization compared with buprenorphine.
Reported IRR for pain-related hospitalization favored methadone (approximately 0.64; 95% CI around 0.58–0.70), indicating fewer hospitalizations for pain in the methadone cohort.
The magnitude and precision of the aRD for this outcome were presented but include a wide confidence interval, indicating uncertainty in the absolute difference per 1,000 person-years.

Outcomes related to survival and safety

All-cause mortality did not differ meaningfully between methadone and buprenorphine in adjusted analyses, with an HR near 1.0 (approximately 1.06; 95% CI around 0.81–1.39).
The corresponding absolute risk difference for mortality was small and encompassed no clear advantage for either treatment in the provided interval.

Sensitivity analyses and consistency

Findings were reported as aligned across intention-to-treat and per-protocol analyses, supporting internal consistency of the comparative signal for pain-related hospitalizations.
The authors note that the observed patterns could reflect differences in patient populations, dosing regimens, pharmacology, and care settings that cannot be disentangled with the Medicare dataset alone.

Limitations and interpretation caveats

The study acknowledges unmeasured confounding as a primary limitation, along with limited generalizability beyond the Medicare population and the included settings.
The observed favorable pain-related signal with methadone should be interpreted cautiously, recognizing potential residual confounding and unmeasured practice differences that are not captured in claims data.

Implications for practice and open questions

The analysis provides population-based evidence suggesting different pain-related utilization patterns between methadone and buprenorphine within a comorbid pain and OUD context.
The authors emphasize that results require further investigation to understand whether differences reflect patient selection, dosing, pharmacologic properties, or care environments.