(53) Impact of OAT in Individuals With OUD Who Experienced Overdose in Ontario

Background & Introduction: Opioid use disorder (OUD) contributes to substantial health and economic burdens in Canada. From 2016 to 2024, over 47,000 opioid toxicity deaths occurred nationally, with the majority involving non-pharmaceutical opioids and fentanyl. Opioid agonist therapies (OATs), including methadone, transmucosal buprenorphine (TM-BUP), buprenorphine extended-release (BUP-XR), and sustained-release oral morphine (SROM) are effective, established interventions for the treatment of OUD. However, the comparative overdose (OD) risk for patients on various OATs and in different treatment stages remains insufficiently characterized. This study aimed to evaluate the impact of different OATs on opioid-related fatal and non-fatal ODs in Ontario, Canada, to provide evidence that informs clinical practice and optimize treatment recommendations.

Methods: This retrospective, observational, nested case-control study was conducted using Ontario administrative data from ICES, an independent research institute that maintains a repository of linkable, population-based datasets derived from publicly funded administrative health service records. Patients with OUD initiating OAT (i.e., methadone, TM-BUP, BUP-XR, SROM) between January 1, 2022, and June 30, 2024 were identified via International Classification of Diseases-Canada (ICD-CA) and Drug Identification Number (DIN) codes, and selected into the base cohort. From this cohort, cases (patients with either fatal or non-fatal OD events) and controls (no OD events) were selected and matched (1:10) on age, sex, and time at risk for OD. The index date was the first non-fatal or fatal OD event. Case cohorts were not mutually exclusive, with patients experiencing a non-fatal OD and a subsequent fatal OD eligible for inclusion in both. Demographic and clinical characteristics were summarized descriptively. Conditional logistic regression was used to estimate unadjusted (for variables other than age, sex, and time between cohort entry and event date or censoring) odds ratio (OR) of opioid-related fatal and non-fatal OD associated with specific OAT therapies compared with no OAT exposure at index.

Results: In total, 45,243 patients in Ontario were included; 4,109 (9%) had at least one non-fatal OD event and 770 (2%) had a fatal OD event. Adults with fatal OD events were primarily aged 35–49 (41%), while non-fatal OD cases were mostly aged 18–34 (47%). Most cases were male (fatal: 70%; non-fatal: 68%), lived in urban areas (fatal: 89%; non-fatal: 89%) and were concentrated in the lowest income quintile (fatal: 41%; non-fatal: 46%). The most common comorbidities among cases were substance use disorders other than OUD (fatal OD: 75% cases versus 56% controls; non-fatal OD: 80% cases versus 56% controls) and anxiety disorders (fatal OD: 49% cases versus 38% controls; non-fatal OD: 54% cases versus 39% controls).

At index, 83% of fatal and 65% of non-fatal OD cases had no OAT prescription versus 49% and 48% of controls, respectively.

Compared to no OAT exposure at the time of the OD event, unadjusted analyses showed BUP-XR and TM-BUP were associated with lower odds of fatal OD (OR 0.46 [95% confidence interval 0.22–0.97]; OR 0.43 [0.31–0.60], respectively) and non-fatal OD (OR 0.73 [0.61–0.88]; OR 0.28 [0.25–0.31], respectively). SROM was associated with higher odds of fatal OD (OR 1.61 [1.03–2.52]) and non-fatal OD (OR 1.48 [1.27–1.72]) compared to no OAT exposure at index. No statistical significance was observed between no OATs at index and methadone on the odds of fatal and non-fatal ODs (OR 1.04 [0.77–1.44]; OR 1.05 [0.96–1.15]).

The proportion of patients with fatal OD events varied across OATs: ≤2% among those prescribed BUP‑XR, 2% for TM‑BUP, 5% for methadone, 7% for SROM, and ≤4% for multiple OATs. The proportions of non-fatal ODs were: 6% for BUP‑XR, 2% for TM‑BUP, 9% for methadone, 12% for SROM, and 15% for multiple OATs.

As a measure for OAT exposure, time on treatment between base cohort entry and index date was captured. For fatal OD, 15% of cases spent at least 80% of time on OAT versus 40% of controls. For non-fatal OD, 24% of cases spent at least 80% of time on OAT versus 42% of controls.

Discussion & Conclusion: Fatal OD events were more common among individuals aged 35-49, while non-fatal OD events were more prominent in younger populations. The most common comorbidities (substance use disorder and anxiety disorders) were consistent across fatal and non-fatal OD cases, with a slightly higher proportion of non-fatal OD cases having a history of these comorbidities. Compared to no OAT, BUP-XR and TM-BUP were associated with reduced risk of both fatal and non-fatal OD events, whereas SROM was associated with an increased risk. Findings related to methadone were not statistically significant. These findings provide critical insight into the demographic and clinical profiles of OUD patients on OAT who experience overdose in Ontario, highlighting differences in OD risk by OAT type compared to no OAT. These findings emphasize that less time on OATs may be linked to an increased OD risk. These findings highlight an important clinical opportunity: supporting patients to maintain consistent OAT exposure may meaningfully reduce both fatal and non‑fatal OD events. This study is limited by potential inaccuracies of diagnostic and procedural codes in administrative data, incomplete capture of opioid‑related events and OAT use, and no direct measures of OAT adherence.

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