P-016 - (Poster #16) A Retrospective US Commercial Claims Analysis Comparing the Safety Profile of Belbuca and Oral Schedule II Long-Acting Opioids Used for Chronic Low-Back Pain Treatment among Patients Previously Treated with Short-Acting Opioids

Chronic low back pain (cLBP) is a musculoskeletal condition affecting nearly 1 in 4 US adults, with effects that significantly influence the quality of life of those patients. The daily activities of patients diagnosed with cLBP are impaired, usually resulting in inadequate social functioning, unstable mental health, and productivity loss. Despite the significant expenditures directly associated with the healthcare services for cLBP management, there is also an enormous economic burden from the societal perspective.

In general, cLBP treatment depends on disease severity, and US guidelines recommend lifestyle changes, psychotherapies, or exercise programs frequently combined with over-the-counter medications as first-line therapy for patients with low or moderate pain severity. In more severe cases, guideline recommendations are based on opioid and non-opioid analgesics. Opioids are considered an effective therapy to treat severe pain symptoms, but persistent use may lead to a high risk of severe and serious adverse events, especially in patients with high-risk abuse behavior.

Purpose/Objectives:

The safety profile of Belbuca® in the treatment of opioid-naïve cLBP patients was previously evaluated in two US real-world studies. The first study was conducted among commercially insured patients and demonstrated significant safety benefits of Belbuca® over oral schedule II (CII) opioids and buprenorphine patch. A second study exploring safety outcomes in the Medicare population with cLBP demonstrated that Belbuca® had a more favorable safety profile compared to both oral CII opioids and buprenorphine patch. There are no real-world studies that compare Belbuca® safety characteristics to oral CII long-acting opioids (LAO) in cLBP patients.

The objective of this study was to explore the safety characteristics of Belbuca® and oral CII LAO among cLBP patients who were previously treated with oral CII short-acting opioids (SAO). The primary safety outcomes for Belbuca® and LAO treatment were treatment-emergent adverse events (TEAEs), recorded during the treatment period and reported per 1,000 person-years.

Methods:

This study was conducted using the US Merative MarketScan® database (January 2019 to December 2023). The first date of Belbuca® or oral CII LAO prescription was identified as the index date. The observational period consisted of the 6-month pre- and 12-month post-index periods. Adult patients were required to have at least two low back pain diagnoses and at least one SAO prescription in the pre-index period. The positive history of TEAEs was evaluated during the prolonged pre-index period (from the first date of healthcare coverage to the index date, with a minimum of 6 months duration). Only events among patients without a positive history of the respective event were considered TEAEs. Patients with a gap in healthcare coverage and with cancer and HIV diagnoses during the observational period were excluded. Switching between Belbuca® and LAO treatments was not allowed.

The main outcomes were all-grade and serious TEAE rates reported as incidence rate ratios (IRR). Events requiring emergency department or hospitalization management were considered serious. For TEAEs that occurred in one cohort, the rates were compared using absolute incidence rate difference (IRD). Propensity-score matching (PSM) was employed to balance differences in patients’ characteristics and mitigate their impact on study outcomes.

Results:

The non-matched sample consisted of 3,350 patients (1,331 Belbuca® patients and 2,019 LAO patients). After the PSM, differences between cohorts were well-balanced, and the final study sample consisted of 964 patients in the Belbuca® cohort matched to 964 LAO patients.

Considering all-grade TEAEs in the matched study sample, significantly higher rates of CNS- (IRR 0.75, p=0.002), GIT- (IRR 0.79, p=0.009), and skin-related TEAEs (IRR 0.57, p< 0.001) were observed in the LAO cohort, while cardiac-related TEAEs were more frequent among Belbuca® patients (IRR 1.66, p=0.022). Significantly lower incidence rates of all-grade hypotension (IRR 0.19, p=0.017), dizziness (IRR 0.61, p=0.006), seizures (IRR 0.24, p< 0.001), syncope (IRR 0.41, p=0.020), cerebrovascular accident (IRR 0.50, p=0.013), nausea/vomiting (IRR 0.53, p=0.002), constipation (IRR 0.56, p=0.001), anorexia/appetite loss (IRR 0.48, p=0.049), and cellulitis (IRR 0.42, p< 0.001) were reported in the Belbuca® patients. On the other hand, lower rates of all-grade coronary artery disease (IRR 2.20, p=0.029), hypertension (IRD 26.71 per 1,000 person-years, p=0.001), somnolence (IRR 4.74, p=0.032), confusion (IRR 1.75, p=0.040), abdominal pain (IRR 1.43, p=0.034), and pneumonia (IRR 1.96, p=0.033) were noted among LAO patients.

Patients treated with Belbuca® experienced significantly less CNS- (IRR 0.61, p=0.003), OUD- (IRR 0.46, p=0.015), GIT- (IRR 0.49, p=0.001), and skin-related (IRR 0.38, p=0.016) serious TEAEs, while serious cardiac-related (IRR 3.55, p=0.001) and hormonal TEAEs (IRD 9.71 per 1,000 person-years, p=0.040) were more common during Belbuca® treatment. Significantly lower occurrence of serious seizures (IRR 0.18, p< 0.001), cerebrovascular accident (IRR 0.45, p=0.018), opioid abuse/dependence (IRR 0.47, p=0.025), nausea/vomiting (IRR 0.28, p=0.001), constipation (IRR 0.12, p=0.015), and cellulitis (IRR 0.29, p=0.004) were observed in the Belbuca® cohort. The incidence rates of serious coronary artery disease (IRR 4.47, p=0.003), hypertension (IRD 14.57 per 1,000 person-years, p=0.012), somnolence (IRD 9.71, p=0.040), dehydration (IRR 2.37, p=0.039), and adrenal insufficiency (IRD 9.71 per 1,000 person-years, p=0.040) were significantly lower in LAO patients.

Conclusions/Implications for future research and/or clinical care:

This retrospective study demonstrated that oral CII LAO treatment was associated with significantly higher incidence rates of 9 all-grade TEAEs (hypotension, dizziness, seizures, syncope, cerebrovascular accident, nausea/vomiting, constipation, anorexia/loss of appetite, and cellulitis). Conversely, Belbuca® patients had higher incidence rates of 6 all-grade TEAEs (coronary artery disease, hypertension, somnolence, confusion, abdominal pain, and pneumonia).

Belbuca® was associated with significantly lower incidence rates of 6 serious TEAEs (seizures, cerebrovascular accident, opioid abuse/dependence, nausea/vomiting, constipation, and cellulitis). However, significantly higher incidence rates were observed for 5 TEAEs (coronary artery disease, hypertension, somnolence, dehydration, and adrenal insufficiency) in the Belbuca® cohort.

This data is primarily collected for billing purposes, henceforth, many data entry errors may have occurred, with a lack of data related to the low back pain severity and chronicity. Another limitation is associated with the underlying causes of TEAEs. Although TEAEs were captured during treatment period, there were still some cases that may not be related to the index treatment.

This is the first real-world evidence study evaluating the safety profiles of Belbuca® and oral CII LAO among SAO-experienced cLBP patients. It provides a significant overview of the most common TEAEs, which may suggest a slightly improved safety of Belbuca® treatment.