Patterns of Buprenorphine Initiation Treatment for Opioid Use Disorder and Association with Opioid-related Overdose Deaths

Background: Buprenorphine is highly effective in treating opioid use disorder (OUD) and significantly reduces all-cause and opioid-related mortality.

Objectives: To evaluate associations between characteristics of transmucosal (TM) buprenorphine treatment within 30 days of initiation and incidence of opioid-related overdose deaths.

Methods: Using prescription monitoring data, we identified a cohort of adult Kentucky residents who initiated TM buprenorphine treatment for OUD from Jan 2017 to Nov 2019 and did not die or switch to long-acting injectable (LAI) buprenorphine within 30 days of initiation. The average daily dose of the initial prescription and that during the first 30 days were respectively categorized as ≤ 8 mg, >8 to ≤ 16 mg, and >16 mg. Using the proportion of days covered (PDC) in treatment, patients' adherence within 30 days of initiation was classified as low (PDC < 0.4), moderate (PDC: 0.4-0.8), or high (PDC≥0.8). Patients were followed for 365 days from the index date (day 30 after initiation) to identify if they died. The cause of death was identified from the Kentucky death certificate data. Multivariable Fine and Gray regression models examined the associations between each treatment initiation characteristic and opioid-related overdose death incidence, considering deaths from other causes as competing risks. Adjusted subhazard ratios were reported [aSHR] [95% CI], adjusted for patient demographics and baseline controlled substance use.

Results: Of the 49,857 patients in the cohort, 689 (1.38%) experienced death during the 365-day follow-up, including 227 (0.46%) who died from opioid-related overdoses. The average daily doses of the initial prescription of >8 to ≤16 mg and >16 mg (vs. ≤ 8 mg) were respectively associated with a 43% (aSHR: 0.57 [0.44-0.75]) and 52% (0.48, [0.28-0.82]) decrease in the incidence of opioid-related overdose deaths. Similar associations were found for the average daily dose within 30 days of initiation (>8 to ≤16 mg: aSHR =0.40 [0.31, 0.53]; >16 mg, aSHR=0.30 [0.18, 0.50] (vs. ≤8 mg)). Compared to patients with low adherence, incidence of opioid-related overdose deaths was lower in patients with moderate adherence (aSHR:0.40 [0.23 to 0.67]) only in the first 180 days, and incidence was lower in patients with high adherence during the entire follow-up (days 1 to 180: aSHR: 0.24, [0.16, 0.37]; days 181 to 365: 0.56 [0.36, 0.86]).

Conclusions: Higher average daily dose and higher patients' adherence within 30 days of buprenorphine initiation were associated with lower opioid-related overdose death incidence, suggesting the importance of prescribing decisions and retaining patients in the early stage of buprenorphine treatment for OUD.