Characterizing initiation, use, and discontinuation of extended-release buprenorphine in a nationally representative United States commercially insured cohort

Abstract

Background and aims: While the United States is in the midst of an overdose epidemic, effective treatments are underutilized and commonly discontinued. Innovations in medication delivery, including an extended-release formulations, have the potential to improve treatment access and reduce discontinuation. We sought to assess extended-release buprenorphine discontinuation among individuals with opioid use disorder (OUD) in a real-world, nationally representative cohort.

Setting: United States PARTICIPANTS: Commercially insured individuals initiating one of four FDA-approved medications for opioid use disorder (MOUD) in 2018: extended-release buprenorphine, extended-release naltrexone, mucosal buprenorphine (mono- or co-formulated with naloxone), or methadone.

Measurements: Our primary outcome was medication discontinuation, defined as a gap of more than 14 days between the end of one prescription or administration and the subsequent dose.

Findings: We identified 14,358 individuals initiating MOUD in 2018, including 204 (1%) extended-release buprenorphine, 1,173 (8%) extended-release naltrexone, 12,171 (85%) mucosal buprenorphine, and 810 (6%) methadone initiations. Three months after initiation, 50% (95% confidence interval [CI] 40%-60%) of extended-release buprenorphine, 64% (95% CI 61%-69%) of extended-release naltrexone, 34% (95% CI 33%-35%) of mucosal buprenorphine, and 58% (95% CI 54%-62%) of methadone initiators had discontinued treatment.

Conclusions: Across all treatment groups, medication discontinuation was high, and in this sample of early adopters with limited follow-up time, we found no evidence that extended-release buprenorphine offered a retention advantage compared to other MOUD in real-world settings. Retention continues to represent a major obstacle to treatment effectiveness, and interventions are needed to address this challenge even as new MOUD formulations become available.

Keywords: Extended-release buprenorphine; Medication for opioid Use disorder; Opioid use disorder; Retention.

Figure 1:. Time-to-medication discontinuation among individuals treated for opioid use disorder in a 2018 United States commercially insured population.

This Kaplan–Meier survival curve displays the time to discontinuation for individuals prescribed injectable buprenorphine, injectable naltrexone, mucosal buprenorphine (mono- or co-formulated with naloxone), and methadone. Injectable formulations have no discontinuation prior to 4-weeks, reflecting the fact that once the medication is injected, an individuals is adherent for the duration of the extended-release medication, compared to mucosal buprenorphine, which may be prescribed for different lengths of time, and methadone, which is dispensed daily. The horizontal axis displays the time to discontinuation in days while the vertical axis displays the proportion of the population with a current prescription.

Figure 2:. Histograms of medication uptake by month and medication type in a commercially insured cohort of individuals initiating medication for opioid use disorder in 2018

XR-BUP=Extended-release buprenorphine; XR-NTX=extended-release naltrexone; M-BUP=sublingual buprenorphine (mono- or co-formulated with naloxone). For each histogram, the vertical axis is the percent of total initiations of the given medication that occurred on a given month. For example, of all M-BUP initiations, just under 10% occurred in January.

Figure 3:. Extended-release buprenorphine strength over dosing time in a commercially insured cohort of 204 individuals in 2018