Aims: To compare the real-world effectiveness of extended release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) for the treatment of opioid use disorder (OUD) Design: An observational active comparator, new user cohort study Setting: Medicaid claims records for patients in New Jersey and California, 2016-2019 Participants/Cases: Adult Medicaid patients aged 18-64 years who initiated XR-NTX or SL-BUP for maintenance treatment of OUD and did not use medications for OUD in the 90-days before initiation Comparators: New initiation with XR-NTX versus SL-BUP for the treatment of OUD Measurements: We examined two outcomes up to 180 days after medication initiation, 1) composite of medication discontinuation and death, and 2) composite of overdose and death Findings: Our cohort included 1,755 XR-NTX and 9,886 SL-BUP patients. In adjusted analyses, treatment with XR-NTX was more likely to result in discontinuation or death by the end of follow-up than treatment with SL-BUP: cumulative risk 76% (95% confidence interval [CI] 75%, 78%) versus 62% (95% CI 61%, 63%), respectively (risk difference 14 percentage points, 95% CI 13, 16). There was minimal difference in the cumulative risk of overdose or death by the end of follow-up: XR-NTX 3.8% (95% CI 2.9%, 4.7%) versus SL-BUP 3.3% (95% 2.9%, 3.7%); risk difference 0.5 percentage points, 95% CI -0.5, 1.5. Results were consistent across sensitivity analyses. Conclusions: Longer medication retention is important because risks of negative outcomes are elevated after discontinuation. Our results support selection of SL-BUP over XR-NTX. However, most patients discontinued medication by 6 months indicating that more effective tools are needed to improve medication retention, particularly after initiation with XR-NTX, and to identify which patients do best on which medication.

Declarations of competing interest: Dr. Nunes has served as an investigator on NIH-funded studies that received donated medication or digital therapeutics from Alkermes, Braeburn, Camurus, Indivior, Chess Health, and Pear Therapeutics, and has served as a consultant without compensation to Alkermes, Camurus, Indivior, and Pear Therapeutics. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

This study was funded by NIH NIDA 5R01DA056407

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The IRB of Columbia University gave ethical approval for this work

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Research data are not shared. The data that support the findings of this study are available from the Research Data Assistance Center. Restrictions apply to the availability of these data, which were used under license for this study. All code and data definitions are available at https://github.com/CI-NYC.

https://github.com/CI-NYC