Treatment Characteristics of Chronic Low Back Pain Patients Treated with Belbuca® and Buprenorphine Transdermal Patches: A Retrospective US Commercial Claims Analysis

Abstract Title: Treatment Characteristics of Chronic Low Back Pain Patients Treated with Belbuca® and Buprenorphine Transdermal Patches: A Retrospective US Commercial Claims Analysis

Background:

The chronic low back pain (cLBP) diagnosis is associated with a high economic disease burden and a high impact on a patient’s quality of life. Greater severity of pain is common in the cLBP population, which emphasizes the need for emergent and effective treatment.¹ Although clinical guidelines recommend a wide range of medications from different therapeutic classes and other types of therapy, there is still no ideal treatment option for this condition.^2-4 Most patients are supplied with opioids for cLBP management, but severe and serious adverse events often follow their frequent use.⁵

Buprenorphine is a Schedule III partial µ-opioid receptor agonist with comparable efficacy to Schedule II opioid medications.⁶ Buprenorphine buccal film (Belbuca®) and transdermal patch (BTP) products ensure proper drug bioavailability and are proven to be effective in chronic pain management with much better safety characteristics than other opioids.^7,8

Purpose/Objectives:

This study aimed to explore buprenorphine and opioid treatment characteristics and prescribing patterns. Additionally, the changes in opioid utilization measures were investigated and compared before and after Belbuca® or BTP initiation.

Method:

This retrospective analysis was conducted on the Merative MarketScan® database of commercially insured patients from January 01, 2018 to December 31, 2021. The study’s observational period consisted of 6-month pre- and post-index periods. The index date was deemed the first date of buprenorphine prescription (Belbuca® or BTP). Belbuca® and BTP medications were identified based on the corresponding national drug codes (NDCs). Adult patients diagnosed with cLBP were included in the study analysis. Two low back pain diagnoses were required during the pre-index period to ensure disease chronicity. Patients were excluded if they had gaps in healthcare and pharmaceutical coverage or had been diagnosed with opioid use disorder during the observational period.

Demographic characteristics of the study sample were assessed on the index date, while patients’ clinical characteristics were observed during the pre-index periods. Propensity-score matching (PSM) analysis using the nearest-neighbor algorithm was performed to minimize the selection bias, and balance observed differences in patients’ characteristics. The analysis focused only on oral opioid and non-opioid rescue medications identified with the corresponding NDCs. Non-opioid rescue medications (NRM) were selected based on the cLBP treatment guidelines.^2-4 The main study outcomes were buprenorphine and rescue medication treatment characteristics in cLBP patients, treatment duration, number of prescriptions, daily doses, and switching rates. To assess the impact of buprenorphine treatment on rescue medication utilization, treatment characteristics were also evaluated in the pre-index period. The trend of reduced or increased rescue medication usage was determined by comparing study outcomes in a 6-month post-index period to a 6-month pre-index period.

Continuous variables were analyzed with an independent sample t-test (between-group differences) and reported as mean values with standard deviation. Categorical variables were analyzed with the chi-square test of independence and summarized as numbers and proportions of the sample. Between-group differences regarding the reduction or increase in opioid utilization after buprenorphine treatment initiation were validated with mixed model ANOVA.

Results:

There were 17,439 patients initially prescribed Belbuca® or BTP. After applying the study inclusion criteria, the non-matched population consisted of 3,747 patients. A total number of 2,602 patients (1,301 in each cohort) were identified in the final sample of matched patients by performing PSM analysis.

Demographic and clinical characteristics were well-balanced between the study cohorts, and no differences were observed (p >0.05). During the pre-index period, Belbuca® patients were treated with a higher number of opioid prescriptions (5.7 vs. 4.9, p< 0.001), over a longer opioid treatment period (104.2 vs. 89.8 days, p< 0.001), and lower number of NRM prescriptions (4.8 vs. 5.2, p=0.021) than BTP patients. In addition, observed daily morphine milligram equivalents (MMEs) were higher among Belbuca®-treated patients (51.5 vs. 39.8, p< 0.001). Following initiation of buprenorphine treatment, Belbuca® patients were on higher average buprenorphine doses compared to the BTPs (501.7 vs. 270.9 mcg, p< 0.001), but with a lower number of buprenorphine prescriptions (3.4 vs. 3.7, p=0.011) and treated over a shorter period (87.2 vs. 91.9 days, p=0.043). The switching rate from BTPs to Belbuca® was higher than vice-versa (11.5% vs. 3.8%, p< 0.001), most likely due to BTPs dosing limitations. Time-to-switch and buprenorphine daily dose before the switch did not differ between cohorts.

Both cohorts demonstrated a significant reduction in opioid usage over the 6 months after buprenorphine treatment initiation versus pre-index opioid characteristics (all p< 0.001). Compared to 6-month pre-index opioid utilization, the introduction of Belbuca® treatment reduced utilization of all opioid prescriptions (5.7 vs. 4.6) including both short-acting (4.8 vs. 4.1) and long-acting opioids (0.9 vs. 0.5), decreased daily MMEs (51.5 vs. 38.9), and shortened duration of opioid treatment (104.2 vs. 90.8 days). The number of NRM prescriptions in the post-index was also significantly decreased by Belbuca® initiation compared to the pre-index period (4.8 vs. 4.6, p=0.008). Similar trends were observed in the BTP cohort. Additionally, a between-group comparison of changes in treatment outcomes demonstrated a greater reduction among Belbuca® patients compared to BTPs in a number of all opioid prescriptions (-1.1 vs. -0.7, p=0.012), particularly long-acting opioids (-0.4 vs. -0.2, p< 0.001), total daily MMEs (-12.6 vs. -7.3, p< 0.001), and opioid treatment duration (-13.4 vs. -7.6 days, p=0.022). The reduction in short-acting opioid and NRM utilization after buprenorphine initiation was similar between study cohorts.

Conclusions: Belbuca® treatment initiation led to a significantly greater reduction in opioid utilization measures (number of all opioid and long-acting opioid prescriptions, daily MME, and opioid treatment duration) than the introduction of BTPs, despite having a substantially shorter Belbuca® treatment duration and fewer number of Belbuca® prescriptions during the follow-up. Data imply that Belbuca® was initiated in cLBP patients with greater pain severity since they had greater opioid burden (highly potent analgesics) with lower utilization of NRM (less potent analgesics) over the pre-index period and higher buprenorphine daily doses during the post-index period. In addition, a significantly higher proportion of patients switched from the BTPs to Belbuca® treatment, perhaps indicating more flexible dosing with less rescue medications and fewer MMEs in cLBP management. Further studies should evaluate the safety and tolerability of buprenorphine and opioid medications among cLBP patients to fully depict the risk-benefit profile of these treatment options.

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