P-010 - (Poster #10) Treatment Characteristics and Safety of Belbuca, Buprenorphine Patch, and Oral Schedule II Opioid Treatments among Chronic Low Back Pain Patients without Positive History of Opioid-Use Disorder: A Retrospective US Commercial Claims Analysis

Chronic low back pain (cLBP) is a pain condition that affects up to 40% of the adult population in the US during their lifetime. The incidence and prevalence of cLBP increase with age and it is estimated that nearly 6% of all emergency department visits are attributed to cLBP. In patients diagnosed with cLBP, quality of life is significantly impacted by many obstacles in daily activities and social functioning, resulting in a huge economic burden from a societal perspective. The most recent data suggests that total cLBP-related healthcare costs reach $1.8 billion within the first year of diagnosis.

Depending on the severity of cLBP, US guidelines recommend different treatment options. First-line treatments for patients with cLBP of low to moderate severity include lifestyle changes, psychotherapies, exercise programs, and over-the-counter medications, while patients with severe pain commonly require a combination of opioid and non-opioid analgesics. Although opioids are considered an effective treatment option, persistent non-medical use is frequently followed by severe and serious adverse events, including overdose and opioid misuse.

Purpose/Objectives:

In the previously conducted real-world evidence studies in the US, patients diagnosed with cLBP who were treated with Belbuca^® (buprenorphine buccal film formulation) showed a favourable safety profile relative to other opioid classes. Belbuca^® demonstrated lower rates of treatment-emergent adverse events (TEAEs) among commercially insured and Medicare patients diagnosed with cLBP. In both populations, patients treated with oral CII opioids and buprenorphine patches (transdermal buprenorphine) had higher incidence rates of more TEAEs than Belbuca^® patients.

The objective of this retrospective study was to evaluate and compare the safety characteristics of cLBP patients without a recent positive history of opioid use disorder (OUD) or opioid treatment. The treatment characteristics (utilization rates of other rescue medications) were evaluated as secondary outcomes. The study outcomes were assessed among cLBP patients treated with Belbuca^® and compared to patients treated with oral CII opioids, and the buprenorphine patch.

Methods:

This retrospective study was conducted using the Merative MarketScan^® database of commercially insured US patients from January 2019 to December 2023. Using the national drug codes, the first date of a prescription with Belbuca^®, buprenorphine patch, or oral CII opioid was designated as the index date. The observational period covered a 6-month pre-index period and a follow-up period that lasted until the end of index treatment or continuous healthcare coverage. The requirements were two low back pain diagnoses and no OUD in the pre-index period and continuous healthcare coverage during the observational period. Additionally, patients assigned to the CII opioid cohort had no prior or concomitant buprenorphine prescriptions, while concomitant CII opioid treatment during the post-index period was allowed for buprenorphine patients.

The main outcomes were serious TEAE rates reported as incidence rate ratios (IRR). Only 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) per 1,000 person-years. The secondary outcomes were utilization rates of opioid and non-opioid rescue medications during the follow-up. Propensity-score matching (PSM) was employed to balance differences in patients’ characteristics and minimize their impact on study outcomes.

Results:

The non-matched sample consisted of 180,565 patients (357 Belbuca^® patients, 481 buprenorphine patch patients, and 179,727 oral CII opioid patients). After the PSM, 341 Belbuca^® patients were matched to 1,321 opioid patients. The sub-analysis (Belbuca^® to buprenorphine patch) yielded 321 matched patients per cohort.

There were no serious TEAEs associated with higher occurrence in the Belbuca^® compared to oral CII opioids. Belbuca^® treatment was associated with significantly lower rates of serious opioid abuse/dependence (IRD -33.76 per 1,000 person-years, p=0.032), osteoarthritis (IRD -78.77 per 1,000 person-years, p=0.001), urinary discomfort (IRD -146.28 per 1,000 person-years, p< 0.001), seizures (IRR 0.11, p=0.019), dehydration (IRR 0.13, p=0.003), abdominal pain (IRR 0.25, p< 0.001), and nausea/vomiting (IRR 0.30, p=0.001). In Belbuca^®, 42.2% of patients used short-acting opioids (SAO) and 1.8% used long-acting opioids (LAO) during follow-up. In the opioid cohort, 99.8% used SAO and only 1.1% had LAO during follow-up. Regarding non-opioid rescue medications, Belbuca^® patients mostly utilized gabapentinoids (39.6% vs. 20.0% in the opioid cohort, p< 0.001), while opioid patients mainly used non-steroid anti-inflammatory drugs (NSAIDs) (36.9% vs. 34.9% in Belbuca^®, p=0.485). A significantly higher proportion of patients in Belbuca^® cohort had topiramate (6.7% vs. 2.5%, p< 0.001) and duloxetine (16.4% vs. 5.8%, p< 0.001) prescriptions.

The sub-analysis compared incidence rates of serious TEAEs between Belbuca^® and buprenorphine patch cohorts. Belbuca^® demonstrated higher rates of serious coronary artery disease (IRD 39.01 per 1,000 person-years, p=0.035), cholecystitis (IRD 39.01 per 1,000 person-years, p=0.035), and headache (IRD 39.01 per 1,000 person-years, p=0.035). However, buprenorphine patch cohort had higher incidence rates of serious QT prolongation (IRD -52.78 per 1,000 person-years, p=0.009), opioid abuse/dependence (IRD -184.75 per 1,000 person-years, p< 0.001), confusion (IRR 0.10, p=0.007), hypertension (IRR 0.22, p=0.043), and cellulitis (IRR 0.41, p=0.011). No differences between Belbuca^® vs. buprenorphine patches were observed in proportions of patients who used SAO (41.7% vs. 38.6%, p=0.421) and LAO (1.9% vs. 1.6%, p=1.000) during follow-up. The non-opioid rescue medications utilization rates were similar between Belbuca^® and buprenorphine patch patients (61.4% vs. 59.2%, p=0.572), with gabapentinoids (38.9% vs. 39.3%, p=0.936) and NSAIDs (34.9% vs. 33.6%, p=0.739) as being the most utilized medications.

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

This real-world evidence study within the commercially insured opioid-naïve cLBP patients without a positive history of OUD demonstrated a higher occurrence of serious TEAEs in the oral CII opioid cohort compared to Belbuca^®. Oral CII opioid treatment was associated with significantly higher incidence rates of 7 serious TEAEs (opioid abuse/dependence, osteoarthritis, urinary discomfort, seizures, dehydration, abdominal pain, and nausea and vomiting), while no serious TEAEs were significantly more common in the Belbuca^® cohort. On the other hand, Belbuca^® patients had higher utilization rates of non-opioid rescue medications, especially gabapentinoids, topiramate, and duloxetine.

In comparison with the buprenorphine patch cohort, Belbuca^® was associated with significantly lower incidence rates of 5 serious TEAEs (opioid abuse/dependence, QT prolongation, confusion, hypertension, and cellulitis). Greater incidence rates in the Belbuca^® cohort were observed only for 3 TEAEs (coronary artery disease, cholecystitis, and headache). There were similar utilization rates of opioid and non-opioid rescue medications between Belbuca^® and buprenorphine patch patients.