Economic and Treatment Burden of Chronic Low-Back Pain Patients Transitioning from Short-Acting to Long-Acting Opioids or Buprenorphine Buccal Film: US Claims Analysis

Abstract

Introduction

This study aimed to assess economic burden and treatment characteristics of patients with chronic low-back pain (cLBP) transitioning from oral Schedule II (CII) short-acting opioids (SAO) to oral CII long-acting opioids (LAO) or Belbuca^® (buprenorphine buccal film, BBF).

Methods

Merative MarketScan^® commercial US claims (2019–2023) were retrospectively analyzed. Index date was the first BBF or LAO prescription date. The observation covered 6-month pre-index and 12-month follow-up periods. Patients were adults with ≥ 2 low-back pain and ≥ 1 SAO prescription pre-index claims. Cases with BBF-LAO switching, coverage gap, or cancer/HIV were excluded. Economic burden and treatment characteristics were explored during follow-up. Rescue medication utilization trends were also analyzed (6-month pre-index vs. 6-month follow-up). Propensity-score matching minimized the impact of patient characteristics.

Results

Study sample had 964 patients per cohort. Despite higher prescription costs in BBF ($10,417 vs. $8238, p = 0.007), total and cLBP-related costs were similar. BBF had fewer outpatient visits (33.1 vs. 35.4, p = 0.038), hospitalizations (0.2 vs. 0.3, p = 0.041), cLBP-related hospitalizations (0.04 vs. 0.08, p = 0.013), and shorter cLBP-related hospital stay (0.14 vs. 0.33 days, p = 0.023). BBF also had fewer patients with ED visits (36.9% vs. 41.6%, p = 0.036) and cLBP-related hospitalizations (3.5% vs. 6.1%, p = 0.008).

Adherence and treatment duration between cohorts were similar, with fewer prescriptions in BBF (5.8 vs. 6.5, p = 0.003). Trends showed BBF had greater decreases in SAO treatment duration (− 15.4 vs. − 2.2 days, p < 0.001), prescription counts (− 0.9 vs. − 0.3, p < 0.001), and daily morphine milligram equivalents (− 9.7 vs. − 6.1, p = 0.015). However, more BBF-treated patients had buprenorphine patches (8.2% vs. 3.3%, p < 0.001) with more patch prescriptions (0.3 vs. 0.1, p < 0.001) and longer treatment duration (8.9 vs. 2.6 days, p < 0.001).

Conclusion

Study findings demonstrated similar healthcare expenditures between patients with cLBP transitioning from SAO to BBF and to LAO. Yet, initiating BBF may have lowered healthcare resource utilization and decreased further SAO utilization.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40122-026-00815-0.

Plain Language Summary

This study compared two treatments for adults with chronic low-back pain. All participants were using short-acting opioid pills. Researchers wanted to find out how starting a different medication, a long-acting opioid pill or a buprenorphine buccal film (brand name Belbuca), affected healthcare costs, the use of medical services, and the use of other pain medications. Researchers analyzed the health insurance claims of a large group of US patients. They compared two matched groups—one started treatment with buprenorphine buccal film and the other with a long-acting opioid pill. The study then tracked these patients for 1 year, looking at their medical costs, how often they needed medical services, and their use of other pain medications. While the prescription costs for the buprenorphine buccal film group were higher, the total healthcare costs for both groups were similar. However, the group using buprenorphine buccal film had fewer outpatient visits, fewer hospitalizations (especially those related to their back pain), and fewer visits to the emergency room. This group also had a shorter duration of hospital stay associated with the low-back pain. Patients who started buprenorphine buccal film also significantly reduced their use of the short-acting opioid pill, but used more buprenorphine patches than the other group. Both groups had similar durations of treatment and showed similar levels of adherence, meaning they took their medication as prescribed for a similar length of time.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40122-026-00815-0.

Key Summary Points

Why carry out this study?

Long-term therapy with full µ-opioid agonists is commonly prescribed treatment in US clinical practice for patients with chronic low-back pain of moderate or higher severity, but is also associated with serious safety concerns.

The updated treatment guidelines recommend buprenorphine, a partial µ-opioid agonist with preserved efficacy and a more favorable safety profile than full agonists, as an alternative for full µ-opioid agonists regarding long-term, chronic, non-cancer pain management in the USA.

This retrospective insurance claims analysis aimed to compare economic burden and treatment characteristics of adults with chronic low-back pain who were previously treated with short-acting full µ-opioid agonists and are transitioning to long-acting full µ-opioid agonists or to Belbuca® (buprenorphine buccal film formulation).

What was learned from this study?

One year follow-up pointed out that transitioning to buprenorphine buccal film was associated with similar total healthcare costs (any-cause and low-back pain-related), lower healthcare resource utilization (outpatient, inpatient, and emergency department), similar treatment duration and adherence, greater decrease in utilization of concomitant short-acting full µ-opioid agonists, similar utilization of non-opioid rescue medications, and more common concomitant use of buprenorphine transdermal patches than transitioning to long-acting full µ-opioid agonists in adults with chronic low-back pain.

This study showed that adults with chronic low-back pain who initiate buprenorphine buccal film require fewer healthcare services, suggesting a lower economic burden for patients, and use significantly less short-acting full µ-opioid agonists than those who initiate long-acting full µ-opioid agonists, representing a treatment approach with a better safety profile that should be evaluated in future studies.

Introduction

Low-back pain (LBP) is a common and complex diagnosis associated with a high impact on quality of life and substantial economic burden for disease management. The Global Burden of Disease data shows that this diagnosis accounts for approximately 4.3 million years lived with disability per annum in the USA [1]. There are no differences between male patient and female patient groups in the general US population regarding the occurrence of LBP. However, female patients are at a higher risk of LBP in the young adult population, while the diagnosis is more common among male patients in the older population [2].

LBP is also linked to a high burden for the health system in general, as it is a common diagnosis requiring frequent services, especially in the primary care settings [3]. These statistics are supported by the fact that one in three patients with LBP experiences moderate or greater pain severity, one in three patients develops chronic LBP (cLBP) within 6 months of the initial diagnosis, and overall the management of this condition ranks among the most expensive treatments in the USA [1, 3, 4].

Non-pharmacological interventions such as spinal manipulation techniques, massages, lifestyle adjustments, and acupuncture with over-the-counter pain medications are recommended as first-line options for cLBP [5–7]. More severe cases require surgical interventions and the utilization of strong analgesic medications. Medication management may include monotherapy or different combinations of short-acting opioids (SAO), long-acting opioids (LAO), atypical opioids such as buprenorphine, and non-opioid rescue medications [6, 7]. Concordant treatment and close follow-up by healthcare professionals are mandatory conditions for the successful treatment of all patients with a cLBP diagnosis [6–8].

Although opioids are effective treatment options for cLBP and other pain conditions, there are major safety concerns associated with their use. Long-term use is associated with the occurrence of serious and severe opioid-related adverse events, including the development of opioid use disorder (OUD) [9, 10]. OUD and opioid-related deaths showed high rates and increasing trends in the USA until 2015–2016, when the Centers for Disease Control and Prevention (CDC) published guidelines on opioid prescribing for chronic pain management. In the following 5-year period (2015–2019), national trends have stabilized and even shown a slight decline [10, 11]. The most recent CDC guideline from 2022 supported and updated the previously established opioid prescribing recommendations with the aim of maintaining the decreasing trends of developing OUD [12]. These guidelines provide evidence-based recommendations on opioid prescribing for acute, subacute, and chronic pain diagnoses outside cancer, palliative, or end-of-life care in the primary healthcare settings [10, 12].

Despite efforts to optimize prescribing, most opioid medications remain closely associated with safety concerns, including overdose risk, and limited evidence supporting long-term efficacy [13]. On the basis of the mechanism of action, most opioids are classified as full µ-opioid agonists (FMOA) with a high potential for developing OUD [12]. However, some opioids, like buprenorphine, possess atypical mechanisms that confer a reduced abuse potential while still providing clinical efficacy. Buprenorphine acts as a partial agonist at µ-opioid receptors and an antagonist at kappa opioid receptors [14, 15]. In addition to its lower risk of abuse, published literature mentioned that buprenorphine showed a ceiling effect on respiratory depression and euphoria, and was associated with the reduction of other adverse events commonly observed with FMOA use [16]. These characteristics support its consideration as an alternative with an improved safety profile relative to FMOA, particularly for long-term management of chronic pain [17]. However, buprenorphine is also associated with an extensive first-pass hepatic metabolism, resulting in a low bioavailability when used orally. Other formulations, including transdermal patches and buccal films, have been developed to overcome this issue [16]. The efficacy of buprenorphine buccal film has been demonstrated in opioid-experienced patients transitioning from FMOA [18].

The primary aim of this study is to investigate economic burden and treatment characteristics among commercially insured patients diagnosed with cLBP in the US healthcare setting. The population of interest is limited to patients with cLBP who transitioned from oral Schedule II (CII) SAO to Belbuca^® (Collegium Pharmaceutical Inc., Stoughton, MA, USA), a buprenorphine buccal film formulation, or to oral CII LAO.

Methods

The research was performed in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) cohort studies recommendations (Supplementary Table S1) [19].

Data Source

This retrospective cohort study was conducted using US insurance claims data from the Merative MarketScan^® Commercial Claims Database (Merative L.P., Ann Arbor, MI, USA). This database consists of medical and drug data for over 293 million individuals, encompassing employees and their spouses and dependents covered by employer-sponsored private health insurance in the USA [20]. The study was performed on insurance data claims from January 01, 2019 to December 31, 2023.

The Merative MarketScan^® insurance claims database used for this analysis complies with the Health Insurance Portability and Accountability Act of 1996 (HIPAA), protecting patients’ privacy and ensuring the confidentiality of personal data. Since all data within the abovementioned database are de-identified, approval of the institutional review board or the ethics committee for conducting the research was not required.

Study Population

The study population was identified on the basis of the inclusion/exclusion criteria to ensure that a homogenous sample of patients was captured.

Inclusion criteria:

• Patients prescribed buprenorphine buccal film or oral CII LAO (first prescription as index date)

• Adult patients (age ≥ 18 years) on the index date

• At least two claims with a diagnosis of low-back pain (LBP) in the 6-month pre-index period

• At least one claim of oral CII SAO medication during the 6-month pre-index period

Exclusion criteria:

• Patients prescribed buprenorphine buccal film within the LAO cohort and vice versa during the 12-month follow-up period

• Malignancy or HIV diagnosis in the observational period (6-month pre- and 12-month follow-up)

• A gap in the continuous healthcare coverage during the observational period

Since patients are transitioning from SAO to buprenorphine buccal film or LAO, they had to be SAO-experienced and were allowed to concomitantly use SAO alongside buprenorphine buccal film and LAO treatments.

Study Design

Patients prescribed buprenorphine buccal film or oral CII LAO were identified in the database using the respective National Drug Codes (NDCs) from the most recent Redbook (Supplementary Tables S2 and S3). The first date of buprenorphine buccal film or oral CII LAO prescription was assigned as the index date. On the basis of the prescribed product on the index date, patients were stratified in two separate cohorts—buprenorphine buccal film and LAO. The observational period consisted of the 6-month pre-index and 12-month follow-up periods. The cLBP criterion was defined as having at least two LBP diagnoses during the 6-month pre-index period, identified via the International Classification of Diseases – Clinical Modification (ICD-10-CM) codes (Supplementary Table S4). Patients were also required to have at least one oral CII SAO in the 6-month pre-index period, captured using the respective NDCs (Supplementary Table S5). Adult patients (at least 18 years of age on the index date) were included in the analysis, while those with a gap in the continuous healthcare and pharmaceutical coverage, malignancy, or HIV diagnosis (identified with ICD-10-CM codes; Supplementary Table S6) during the observational period were excluded. Patients were allowed to have oral CII SAO prescriptions alongside buprenorphine buccal film and oral CII LAO medications during the follow-up but switching between buprenorphine buccal film and oral CII LAO was prohibited (buprenorphine buccal film-treated patients were not allowed to have oral CII LAO prescriptions and vice versa). The study design is presented in Fig. 1.

Fig. 1.

Study design. LAO long-acting opioids, SAO short-acting opioids. No permissions were required for the use of this figure in the manuscript. The authors have purchased dataset for analytics purposes with specific theme that is the title of the manuscript

Outcome Measures

Demographic characteristics of the study sample were captured on the index date, while clinical characteristics were observed in the 6-month pre-index period. The main study outcomes were economic burden and treatment characteristics. Most outcomes were captured during the 12-month follow-up period, except for the trend analysis (within-cohort comparison of the results from the 6-month pre-index period vs. the first 6 months of the follow-up period).

Economic Burden

Economic burden outcome measures included both any-cause and cLBP-related healthcare costs and resource utilization assessed over a 12-month follow-up period. Any-cause healthcare costs were calculated as a sum of total expenditures for all provided services and prescriptions, while cLBP-related costs were calculated as a sum of total expenditures for all services claimed with LBP diagnosis. Healthcare costs were further stratified by setting—outpatient, inpatient, and emergency department (ED)—and compared between the cohorts. The numbers of any-cause and cLBP-related outpatient, ED, and hospitalization visits, as well as the total duration of hospital stays per patient, were the main outcomes that reflected the resource consumption.

Treatment Characteristics

Treatment characteristics outcomes included index treatment and rescue medication utilization measures.

Index Treatment Utilization Measures

Outcomes associated with the index treatment were captured during the 12-month post-index period and included prescription counts, average daily doses, treatment duration, and adherence measures. Adherence was assessed using the medication possession ratio (MPR) and proportion of days covered (PDC) scores. The following formulae were employed to calculate MPR and PDC (Fig. 2).

Fig. 2.

Formulae for MPR and PDC calculation. MPR medication possession ratio, PDC proportion of days covered. No permissions were required for the use of this figure in the manuscript. The authors have purchased dataset for analytics purposes with specific theme that is the title of the manuscript

The denominator was defined as the index treatment duration period (the period between the index date and the latest prescription end date of index medication). The last date of prescription was determined using the prescription date and the number of supply days of that prescription. The difference between MPR and PDC calculations was in the numerator. The MPR was calculated using the sum of all supply periods of the index medication. If there were overlaps between prescriptions, the total sum of supply periods might be longer than the denominator; hence, the result could be an MPR value higher than 1.0. On the other hand, the PDC value was estimated using the sum of days covered by index medication prescription as the numerator. Hence, even if there were prescription overlaps, the PDC value could not exceed the score of 1.0. It was assumed that patients were adherent to the index treatment (buprenorphine buccal film or LAO) if the mean MPR or PDC values were higher than the 0.80 threshold.

Rescue Medications Utilization Measures

Treatment characteristics were also investigated for other opioid and non-opioid rescue medications. During the 12-month post-index period, utilization rates and prescription counts were assessed for the key non-opioid rescue medications identified in the cLBP treatment guidelines, including topiramate, duloxetine, gabapentinoids, and non-steroid anti-inflammatory drugs (NSAID) [6, 7, 21], as well as buprenorphine transdermal patches, and oral CII SAO medications. For oral CII SAO and buprenorphine patches, average daily dose, treatment duration, and time-to-initiation were also reported. The rationale for prescribing oral CII SAO and buprenorphine patches could not be assessed (insufficient efficacy of index medication, switching due to adverse events of index medication, etc.) as there is a lack of such information in the insurance claims databases.

Additionally, rescue medication utilization trends were analyzed for the non-opioid rescue medications and oral CII SAO. This within-cohort trends analysis compared rescue medication utilization measures between the 6-month pre-index period (before starting index treatment) and the first 6 months of the follow-up period (after starting index treatment). Hence, this analysis investigates the impact of prescribing buprenorphine buccal film and LAO on the use of other rescue analgesics. Following the estimation of outcome trends within each study cohort, the changes in utilization levels were also compared between cohorts.

Statistical Analysis

Cases with missing relevant data for patient selection or outcome assessment were excluded from the analysis. Continuous variables were summarized as means and standard deviations, while categorical variables were summarized as numbers and proportions of the sample. Independent t test (continuous variables) and chi-square test of independence (categorical variables) were performed to test the difference between the comparable cohorts. In trends analysis, a paired-sample t test was used to assess the within-cohort differences between continuous variables, and between-cohort comparisons were investigated using an independent sample t test. The trend analysis results were validated with a mixed model of repeated-measures analysis of variance (ANOVA). P values lower than 0.05 implied statistical significance between or within the cohorts.

Propensity score matching (PSM) analysis was used to minimize the selection bias and balance differences between study cohorts. PSM was performed with a 1:1 matching ratio, the nearest-neighbor matching algorithm, a random matching order, and a caliper of 0.001. Demographic characteristics of patients observed on the index date and clinical characteristics observed throughout the 6-month pre-index period were used as a basis for the matching process.

All statistical analyses were performed using the IBM Statistical Package for the Social Sciences (SPSS^®) (International Business Machines Corporation, Armonk, NY, USA), Statistical Analysis System (SAS^®) (SAS Institute Inc., Cary, NC, USA), and MedCalc^® (MedCalc Software Ltd., Ostend, Belgium).

Results

There were 43,378 patients prescribed buprenorphine buccal film or LAO in the database. The final non-matched sample included 3350 patients—1331 patients in the buprenorphine buccal film cohort and 2019 patients in the LAO cohort. The patient selection flow diagram is presented in Fig. 3.

Fig. 3.

Patient selection flow diagram. BBF buprenorphine buccal film, CII Schedule II, LAO long-acting opioids, HIV human immunodeficiency virus. No permissions were required for the use of this figure in the manuscript. The authors have purchased dataset for analytics purposes with specific theme that is the title of the manuscript

Non-matched Population

Demographic and Clinical Characteristics

Patients in the buprenorphine buccal film cohort were younger (49.5 vs. 50.7 years, p < 0.001), more of them were female at birth (64.4% vs. 57.9%, p < 0.001), and more frequently enrolled in consumer-driven health plans compared to the LAO cohort (13.4% vs. 10.7%, p = 0.019). A significantly higher rate of buprenorphine buccal film-treated patients resided in the South (64.8% vs. 52.9%, p < 0.001), while LAO-treated patients were predominant in other regions. Demographics of the non-matched sample are presented in Table 1.

Table 1.

Demographic characteristics of non-matched patients

	BBF (N = 1331)	LAO (N = 2019)	P valuea
Age, mean (SD)	49.5 (8.9)	50.7 (9.0)	< 0.001
Sex, n (%)
Male	474 (35.6)	850 (42.1)	< 0.001
Female	857 (64.4)	1169 (57.9)	< 0.001
Health plan, n (%)
Comprehensive	51 (3.8)	78 (3.9)	0.963
Exclusive provider organization	12 (0.9)	21 (1.0)	0.691
Health maintenance organization	188 (14.1)	306 (15.2)	0.410
Non-capitated point-of-service	75 (5.6)	105 (5.2)	0.585
POS with capitation	4 (0.3)	12 (0.6)	0.308
Preferred provider organization	694 (52.1)	1088 (53.9)	0.321
Consumer-driven health plan	178 (13.4)	216 (10.7)	0.019
High-deductible health plan	111 (8.3)	172 (8.5)	0.855
Unknown	18 (1.4)	21 (1.0)	0.410
Region, n (%)
Northeast	97 (7.3)	219 (10.8)	0.001
North-Central	206 (15.5)	382 (18.9)	0.010
South	863 (64.8)	1069 (52.9)	< 0.001
West	164 (12.3)	347 (17.2)	< 0.001
Unknown	1 (0.1)	2 (0.1)	1.000

BBF buprenorphine buccal film, LAO long-acting opioids, SD standard deviation

^aChi-square test was performed for categorical variables and independent t test for continuous variables

On the basis of the Charlson Comorbidity Index (CCI), buprenorphine buccal film-treated patients had lower comorbidity burden than LAO-treated patients (0.8 vs. 1.0, p < 0.001). Regarding CCI comorbidities, significantly lower rates of peripheral vascular disease (1.7% vs. 3.2%, p = 0.007), peptic ulcer disease (0.5% vs. 1.2%, p = 0.038), diabetes without chronic complications (14.5% vs. 18.0%, p = 0.008), and diabetes with chronic complications (11.0% vs. 14.3%, p = 0.005) were observed in the buprenorphine buccal film cohort. Besides CCI components, buprenorphine buccal film-treated patients had lower comorbidity rates of musculoskeletal disorders (79.6% vs. 82.7%, p = 0.022) and diabetic neuropathy (4.4% vs. 6.5%, p = 0.012). The rates of mental health comorbidities and COVID infection were similar between the study cohorts. Conversely, comorbidities with higher rates among buprenorphine buccal film-treated patients were fibromyalgia (22.5% vs. 19.5%, p = 0.032) and other neuropathies (40.3% vs. 35.3%, p = 0.003). Clinical characteristics of the non-matched sample are presented in Table 2.

Table 2.

Clinical characteristics of non-matched patients

	BBF (N = 1331)	LAO (N = 2019)	P valuea
Charlson Comorbidity Index
0	774 (58.2)	1116 (55.3)	0.100
1	292 (21.9)	386 (19.1)	0.047
2	105 (7.9)	190 (9.4)	0.128
3	83 (6.2)	168 (8.3)	0.025
4+	77 (5.8)	159 (7.9)	0.021
Charlson Comorbidity Index, mean (SD)	0.8 (1.3)	1.0 (1.5)	< 0.001
Charlson Comorbidity Index Components
Myocardial infarction	9 (0.7)	20 (1.0)	0.336
Congestive heart failure	35 (2.6)	73 (3.6)	0.114
Peripheral vascular disease	22 (1.7)	64 (3.2)	0.007
Cerebrovascular disease	37 (2.8)	75 (3.7)	0.141
Dementia	1 (0.1)	7 (0.3)	0.157
Chronic pulmonary disease	220 (16.5)	325 (16.1)	0.740
Rheumatic disease	109 (8.2)	142 (7.0)	0.214
Peptic ulcer disease	7 (0.5)	25 (1.2)	0.038
Mild liver disease	63 (4.7)	116 (5.7)	0.202
Moderate or severe liver disease	3 (0.2)	10 (0.5)	0.267
Diabetes without chronic complications	193 (14.5)	363 (18.0)	0.008
Diabetes with chronic complications	146 (11.0)	288 (14.3)	0.005
Hemiplegia or paraplegia	13 (1.0)	30 (1.5)	0.200
Renal disease	48 (3.6)	90 (4.5)	0.225
Malignancy	0 (0.0)	0 (0.0)	–
Metastatic solid tumor	0 (0.0)	0 (0.0)	–
AIDS/HIV	0 (0.0)	0 (0.0)	–
Mental disorders
Anxiety	507 (38.1)	725 (35.9)	0.200
Bipolar disorder	74 (5.6)	89 (4.4)	0.130
Depression	375 (28.2)	570 (28.2)	0.971
Sleep disorder	200 (15.0)	282 (14.0)	0.393
Psychosis	33 (2.5)	67 (3.3)	0.163
Post-traumatic stress syndrome	52 (3.9)	78 (3.9)	0.949
Chronic pain-specific comorbidities
Joint pain	694 (52.1)	1114 (55.2)	0.085
Musculoskeletal disorders	1059 (79.6)	1670 (82.7)	0.022
Diabetic neuropathy	59 (4.4)	131 (6.5)	0.012
Other neuropathies	537 (40.3)	713 (35.3)	0.003
Spine disorders	920 (69.1)	1425 (70.6)	0.367
Fibromyalgia	300 (22.5)	393 (19.5)	0.032
Other comorbidities
COVID infection	64 (4.8)	85 (4.2)	0.411

BBF buprenorphine buccal film, LAO long-acting opioids, SD standard deviation, AIDS/HIV acquired immunodeficiency syndrome/human immunodeficiency virus

^aChi-square test was performed for categorical variables and independent t test for continuous variables

Matched Population

PSM yielded 1928 patients in the final matched sample with 964 patients in each study cohort. Demographic and clinical characteristics of the study sample were used as a basis for the matching process. Since the matching was successful, none of the assessed demographic and clinical characteristics were likely to not impact the study findings (Supplementary Tables S7 and S8).

Economic Burden

Healthcare Costs

Despite significant prescription cost differences between the buprenorphine buccal film and LAO cohorts ($10,417 vs. $8238, p = 0.007), there were no differences observed in total any-cause healthcare costs ($37,778 vs. $36,663, p = 0.670). Total cLBP-related costs were also similar between study cohorts ($5881 vs. $6134, p = 0.785), without any difference observed in cLBP-related expenditures across different healthcare settings (all p ≥ 0.050). Healthcare expenditures captured during the 12-month follow-up period are presented in Table 3.

Table 3.

Healthcare costs during the 12-month follow-up period among matched patients

Cost category, mean (SD)	BBF (N = 964)	LAO (N = 964)	P valuea
Prescription cost	$10,417 (15,653)	$8238 (19,719)	0.007
Any-cause outpatient cost	$16,069 (38,165)	$15,111 (23,096)	0.505
cLBP-related outpatient cost	$3721 (10,172)	$3694 (10,951)	0.955
Any-cause inpatient cost	$8885 (32,349)	$10,551 (38,429)	0.303
cLBP-related inpatient cost	$2030 (17,425)	$2203 (15,323)	0.817
Any-cause ED-related cost	$2406 (7374)	$2763 (7976)	0.308
cLBP-related ED cost	$129 (767)	$237 (1687)	0.071
Total any-cause cost	$37,778 (58,851)	$36,663 (56,013)	0.670
Total cLBP-related cost	$5881 (20,639)	$6134 (20,230)	0.785

BBF buprenorphine buccal film, LAO long-acting opioids, SD standard deviation, cLBP chronic low-back pain

^aIndependent t test was used to assess the difference

Healthcare Resource Utilization

Almost all patients had at least one any-cause outpatient visit. The average number of any-cause outpatient visits was significantly lower in the buprenorphine buccal film cohort compared to the LAO cohort (33.1 vs. 35.4, p = 0.038). Rates of patients with at least one cLBP outpatient visit were comparable between the cohorts (96.0% vs. 94.3%, p = 0.091), as was the number of cLBP outpatient visits per patient (11.0 vs. 11.8, p = 0.073).

Regarding the ED setting, there were no significant differences between buprenorphine buccal film and LAO cohorts in the number of any-cause (1.1 vs. 1.3, p = 0.365) and cLBP-related ED visits (0.1 vs. 0.1, p = 0.661). However, the proportion of patients who had at least one any-cause ED visit was significantly lower in the buprenorphine buccal film cohort (36.9% vs. 41.6%, p = 0.036), while there was no difference between the rates of patients who had cLBP-related ED visits (6.4% vs. 6.1%, p = 0.778).

The number of any-cause hospitalizations per patient was significantly lower in the buprenorphine buccal film cohort (0.2 vs. 0.3, p = 0.041), while the average duration of hospitalization was similar to the LAO cohort (1.2 vs. 1.5 days, p = 0.150). Regarding cLBP-related hospitalizations, the rate of patients who had at least one corresponding visit was significantly lower in buprenorphine buccal film (3.5% vs. 6.1%, p = 0.008), with fewer hospitalizations per patient (0.04 vs. 0.08, p = 0.013) and shorter average hospital stays (0.14 vs. 0.33 days, p = 0.023).

The results of healthcare resource utilization of buprenorphine buccal film- and LAO-treated patients during the 12-month follow-up period are presented in Table 4.

Table 4.

Resource utilization among matched patients

	BBF (N = 964)	LAO (N = 964)	P valuea
Outpatient visits
Number of outpatient visits, mean (SD)b	33.1 (22.7)	35.4 (27.0)	0.038
Patients with at least one outpatient visit, n (%)	964 (100.0)	963 (99.9)	1.000
Number of outpatient visits, mean (SD)c	33.1 (22.7)	35.4 (27.0)	0.036
Number of cLBP outpatient visits, mean (SD)b	11.0 (9.1)	11.8 (10.2)	0.073
Patients with at least one outpatient cLBP visit, n (%)	925 (96.0)	909 (94.3)	0.091
Number of cLBP outpatient visits, mean (SD)c	11.5 (9.0)	12.5 (10.1)	0.020
Emergency department (ED) visits
Number of ED visits, mean (SD)b	1.1 (2.8)	1.3 (3.0)	0.365
Patients with at least one ED visit, n (%)	356 (36.9)	401 (41.6)	0.036
Number of ED visits, mean (SD)c	3.1 (3.8)	3.0 (4.1)	0.836
Number of cLBP ED visits, mean (SD)b	0.1 (0.6)	0.1 (0.8)	0.661
Patients with at least one cLBP ED visit, n (%)	62 (6.4)	59 (6.1)	0.778
Number of cLBP ED visits, mean (SD)c	1.8 (1.5)	2.1 (2.3)	0.373
Hospitalizations
Number of hospitalizations, mean (SD)b	0.2 (0.6)	0.3 (1.0)	0.041
Total length of hospitalizations (days), mean (SD)b	1.2 (4.4)	1.5 (6.3)	0.150
Patients with at least one hospitalization, n (%)	160 (16.6)	181 (18.8)	0.210
Number of hospitalizations, mean (SD)c	1.4 (0.9)	1.6 (1.7)	0.089
Total length of hospitalizations (days), mean (SD)c	7.0 (8.9)	8.1 (12.5)	0.361
Number of cLBP hospitalizations, mean (SD)b	0.04 (0.21)	0.08 (0.45)	0.013
Total length of cLBP hospitalizations (days), mean (SD)b	0.14 (1.17)	0.33 (2.22)	0.023
Patients with at least one cLBP hospitalization, n (%)	34 (3.5)	59 (6.1)	0.008
Number of cLBP hospitalizations, mean (SD)c	1.1 (0.3)	1.3 (1.3)	0.430
Total length of cLBP hospitalizations (days), mean (SD)c	4.1 (4.8)	5.4 (7.4)	0.373

BBF buprenorphine buccal film, LAO long-acting opioids, SD standard deviation, cLBP chronic low-back pain, ED emergency department

^aChi-square test was performed for categorical variables and independent t test for continuous variables

^bAcross the total sample

^cConsidering only patients who experienced at least one event of interest

Treatment Characteristics

Index Medications

The treatment durations with index medications were similar between buprenorphine buccal film and LAO (156.0 vs. 164.2 days, p = 0.180). Buprenorphine buccal film-treated patients were treated with a significantly lower number of index medication prescriptions (5.8 vs. 6.5, p = 0.003). The average daily dose was 598.1 mcg for buprenorphine buccal film-treated patients and 47.4 MME for patients in the LAO cohort. Adherence evaluation showed similar values between buprenorphine buccal film and LAO for MPR (0.92 vs. 0.91, p = 0.482) and PDC (0.88 vs. 0.89, p = 0.736). The rates of adherent patients (MPR or PDC value of ≥ 0.80) were also similar between cohorts. Treatment characteristics associated with index medications are presented in Table 5.

Table 5.

Treatment characteristics of index medications during the 12-month follow-up period among matched patients

	BBF (N = 964)	LAO (N = 964)	P valuea
Index medication treatment characteristics during 12-month follow-up period
Treatment duration with index medication (days), mean (SD)	156.0 (126.3)	164.2 (140.9)	0.180
Number of index medication prescriptions, mean (SD)	5.8 (4.8)	6.5 (5.4)	0.003
BBF daily dose (mcg), mean (SD)	598.1 (397.9)	–	–
LAO daily dose (MME), mean (SD)	–	47.4 (38.4)	–
Stratification of patients by number of buprenorphine prescriptions, n (%)
1 prescription	295 (30.6)	287 (29.8)	0.691
2 prescriptions	89 (9.2)	108 (11.2)	0.153
3 prescriptions	73 (7.6)	44 (4.6)	0.006
4 prescriptions	46 (4.8)	45 (4.7)	0.914
5 prescriptions	35 (3.6)	27 (2.8)	0.302
6+ prescriptions	426 (44.2)	453 (47.0)	0.217
Adherence measures during index medication supply periodb
Medication possession ratio (MPR)
MPR, mean (SD)	0.92 (0.19)	0.91 (0.21)	0.482
Proportion of patients with MPR ≥ 0.8, n (%)	773 (80.2)	796 (82.6)	0.178
Proportion of days covered (PDC)
PDC, mean (SD)	0.88 (0.17)	0.89 (0.19)	0.736
Proportion of patients with PDC ≥ 0.8, n (%)	751 (77.9)	783 (81.2)	0.071

BBF buprenorphine buccal film, LAO long-acting opioids, SD standard deviation, MME morphine milligram equivalents, MPR medication possession ratio, PDC proportion of days covered

^aChi-square test was performed for categorical variables and independent t test for continuous variables

^bPeriod between the start of the first index medication prescription (index date) and the end of the last prescription of index medication within the 12-month follow-up period

Rescue Medications Utilization

Regarding opioid rescue medication use during the 12-month follow-up period, the proportion of patients who utilized SAO was significantly lower in the buprenorphine buccal film than the LAO cohort (86.1% vs. 92.1%, p < 0.001). The buprenorphine buccal film cohort also had fewer SAO prescriptions per patient (8.9 vs. 9.9, p < 0.001), shorter mean SAO treatment duration (208.3 vs. 226.4 days, p = 0.004), and lower average SAO daily dose (38.2 vs. 50.9 MMEs, p < 0.001). Considering patients who had SAO during 12-month follow-up, buprenorphine buccal film showed significantly longer mean time-to-first SAO prescription (38.2 vs. 24.9 days, p < 0.001).

Buprenorphine patch was more commonly prescribed to buprenorphine buccal film-treated patients during the 12-month follow-up period (8.2% vs. 3.3%, p < 0.001). Patients treated with buprenorphine buccal film had a higher number of buprenorphine patch prescriptions per patient (0.3 vs. 0.1, p < 0.001), longer mean patch treatment duration (8.9 vs. 2.6 days, p < 0.001), and higher average buprenorphine patch daily doses (27.3 vs. 9.6 mcg, p < 0.001). Among patients who received buprenorphine patch prescriptions, the mean time-to-buprenorphine patch prescription was similar between buprenorphine buccal film and LAO cohorts (117.5 vs. 131.3 days, p = 0.551).

The utilization of SAO and buprenorphine patch medications during the 12-month follow-up period is presented in Table 6.

Table 6.

Utilization of opioid rescue medications during a 12-month follow-up period among matched patients

	BBF (N = 964)	LAO (N = 964)	P valuea
Short-acting opioids (SAO)
Number of SAO prescriptions, mean (SD)b	8.9 (6.0)	9.9 (6.1)	< 0.001
SAO treatment duration (days), mean (SD)b	208.3 (141.1)	226.4 (136.0)	0.004
Average daily MME related to SAO, mean (SD)b	38.2 (30.6)	50.9 (38.2)	< 0.001
Patients with at least one SAO prescription, n (%)	830 (86.1)	888 (92.1)	< 0.001
Number of SAO prescriptions, mean (SD)c	10.3 (5.2)	10.7 (5.5)	0.085
SAO treatment duration (days), mean (SD)c	242.0 (122.3)	245.8 (123.7)	0.521
Average daily MME related to SAO, mean (SD)c	44.4 (28.5)	55.2 (36.7)	< 0.001
Time-to-SAO (days), mean (SD)c	38.2 (66.1)	24.9 (51.5)	< 0.001
Buprenorphine patch
Number of buprenorphine patch prescriptions, mean (SD)b	0.3 (1.6)	0.1 (0.9)	< 0.001
Treatment duration (days), mean (SD)b	8.9 (41.9)	2.6 (22.2)	< 0.001
Buprenorphine patch daily dose (mcg), mean (SD)b	27.3 (99.1)	9.6 (56.7)	< 0.001
Patients with at least one patch prescription, n (%)	79 (8.2)	32 (3.3)	< 0.001
Number of buprenorphine patch prescriptions, mean (SD)c	4.2 (3.9)	3.1 (3.7)	0.192
Buprenorphine patch treatment duration (days), mean (SD)c	108.5 (103.4)	78.4 (95.9)	0.148
Average buprenorphine patch daily dose, mean (SD)c	333.1 (134.6)	290.3 (125.4)	0.125
Time-to-buprenorphine patch (days), mean (SD)c	117.5 (108.9)	131.3 (112.0)	0.551

BBF buprenorphine buccal film, LAO long-acting opioids, SAO short-acting opioids, SD standard deviation, MME morphine milligram equivalents

^aChi-square test was performed for categorical variables and independent t test for continuous variables

^bAcross the total sample

^cConsidering only patients who had at least one corresponding prescription during the 12-month follow-up

The investigation of non-opioid rescue medication utilization showed a higher number of duloxetine prescriptions per patient in the buprenorphine buccal film cohort (1.3 vs. 1.0, p = 0.042). Yet, there were no between-cohort differences associated with the use of other non-opioid rescue medications (NSAID, topiramate, and gabapentinoids). Also, the results were similar between buprenorphine buccal film and LAO cohorts for the average number of non-opioid rescue medications prescriptions (8.6 vs. 7.9, p = 0.072) and the rate of patients with at least one corresponding prescription (84.2% vs. 82.7%, p = 0.358). Utilization rates of non-opioid rescue medications during the 12-month follow-up period are presented in Table 7.

Table 7.

Utilization of non-opioid rescue medications during a 12-month follow-up period among matched patients

	BBF (N = 964)	LAO (N = 964)	P valuea
Non-steroidal anti-inflammatory drugs (NSAID)
Number of NSAID prescriptions, mean (SD)b	2.9 (4.5)	2.7 (4.0)	0.273
Patients with at least one NSAID prescription, n (%)	539 (55.9)	532 (55.2)	0.748
Number of NSAID prescriptions, mean (SD)c	5.3 (4.9)	4.9 (4.3)	0.260
Topiramate
Number of topiramate prescriptions, mean (SD)b	0.4 (1.9)	0.4 (1.7)	0.670
Patients with at least one topiramate prescription, n (%)	70 (7.3)	77 (8.0)	0.548
Number of topiramate prescriptions, mean (SD)c	6.0 (4.1)	5.0 (3.7)	0.131
Duloxetine
Number of duloxetine prescriptions, mean (SD)b	1.3 (3.0)	1.0 (2.8)	0.042
Patients with at least one duloxetine prescription, n (%)	221 (22.9)	198 (20.5)	0.204
Number of duloxetine prescriptions, mean (SD)c	5.7 (3.9)	5.1 (4.1)	0.097
Gabapentinoids
Number of gabapentinoid prescriptions, mean (SD)b	3.9 (4.7)	3.8 (4.8)	0.558
Patients with at least one gabapentinoid prescription, n (%)	541 (56.1)	517 (53.6)	0.272
Number of gabapentinoid prescriptions, mean (SD)c	7.0 (4.2)	7.0 (4.5)	0.745
Non-opioid rescue medications (NORM)
Number of NORM prescriptions, mean (SD)b	8.6 (8.0)	7.9 (7.7)	0.072
Patients with at least one NORM prescription, n (%)	812 (84.2)	797 (82.7)	0.358
Number of NORM prescriptions, mean (SD)c	10.2 (7.7)	9.6 (7.5)	0.122

BBF buprenorphine buccal film, LAO long-acting opioids, NSAID non-steroidal anti-inflammatory drugs, SD standard deviation, NORM non-opioid rescue medications

^aChi-square test was performed for categorical variables and independent t test for continuous variables

^bAcross the total sample

^cConsidering only patients who had at least one corresponding prescription during the 12-month follow-up

Trends of Rescue Medications Utilization

The results comparing opioid and non-opioid rescue medication use between cohorts for the 6-month pre-index vs. the first 6 months of the follow-up period are reported in Supplementary Tables S9 and S10. The buprenorphine buccal film and LAO cohorts had a similar pre-index SAO burden (all p ≥ 0.050), except for the significantly lower average SAO daily doses observed in the buprenorphine buccal film cohort (45.8 vs. 55.4 MMEs, p < 0.001). Utilization measures of non-opioid rescue medications were also similar between cohorts during the pre-index period (all p ≥ 0.050), except for the higher number of duloxetine prescriptions per patient in the buprenorphine buccal film cohort (0.7 vs. 0.5, p = 0.027). Conversely, during the first 6 months after initiation of index treatment, the LAO cohort demonstrated a greater SAO burden. The buprenorphine buccal film cohort had significantly lower rates of patients prescribed SAO (81.4% vs. 89.0%, p < 0.001), a lower number of SAO prescriptions per patient (4.6 vs. 5.3, p < 0.001), shorter mean SAO treatment duration (102.9 vs. 112.8 days, p = 0.002), and lower average SAO daily doses (36.1 vs. 49.4 MMEs, p < 0.001). For non-opioid rescue analgesics, there were no between-cohort differences in the 6-month follow-up period except for duloxetine. A higher rate of buprenorphine buccal film-treated patients received duloxetine (20.1% vs. 16.1%, p = 0.021) and had more duloxetine prescriptions per patient (0.7 vs. 0.5, p = 0.035).

Rescue medication utilization trends in the buprenorphine buccal film cohort demonstrated a decrease in SAO use after initiation of buprenorphine buccal film treatment. Compared to the 6-month pre-index period, the 6-month follow-up period showed a decrease in the buprenorphine buccal film cohort for the number of SAO prescriptions per patient of 0.9 prescriptions (p < 0.001), average SAO daily dose of 9.7 MME (p < 0.001), and mean SAO treatment duration of 15.4 days (p < 0.001). Non-opioid rescue medication utilization remained stable in the buprenorphine buccal film cohort (p = 0.350). In the LAO cohort, SAO utilization also decreased after starting index treatment. There were significant decreases in the number of SAO prescriptions per patient by 0.3 prescriptions (p = 0.011) and in the average SAO daily dose by 6.1 MME (< 0.001). However, the 2.2-day decrease in mean SAO treatment duration was not statistically significant (p = 0.252). Non-opioid rescue medication utilization trends were also stable in the LAO cohort (p = 0.103). The results of opioid and non-opioid utilization trends within buprenorphine buccal film and LAO cohorts are reported in Table 8.

Table 8.

Trends in rescue medications utilization (6-month follow-up period vs. 6-month pre-index period) within the study cohorts among matched patients

	6-month pre-index period	6-month post-index period	Mean differencea	P valueb
BBF (N = 964)
Non-opioid rescue medications (NORM)
Number of NORM prescriptions, mean (SD)	4.5 (4.1)	4.4 (4.4)	− 0.1	0.350
Short-acting opioids (SAO)
SAO treatment duration (days), mean (SD)	118.3 (59.3)	102.9 (70.1)	− 15.4	< 0.001
Number of SAO prescriptions, mean (SD)	5.5 (2.7)	4.6 (3.2)	− 0.9	< 0.001
SAO daily dose (MME), mean (SD)	45.8 (31.6)	36.1 (32.1)	− 9.7	< 0.001
LAO (N = 964)
Non-opioid rescue medications (NORM)
Number of NORM prescriptions, mean (SD)	4.3 (4.1)	4.1 (4.2)	− 0.2	0.103
Short-acting opioids (SAO)
SAO treatment duration (days), mean (SD)	115.0 (61.2)	112.8 (66.3)	− 2.2	0.252
Number of SAO prescriptions, mean (SD)	5.6 (3.1)	5.3 (3.3)	− 0.3	0.011
SAO daily dose (MME), mean (SD)	55.4 (41.0)	49.4 (38.4)	− 6.1	< 0.001

BBF buprenorphine buccal film, NORM non-opioid rescue medications, SAO short-acting opioids, MME morphine milligram equivalents, LAO long-acting opioids

^aThe difference between the 6-month follow-up and pre-index periods (negative values represent a decreasing trend, while the positive values represent an increasing trend in outcome measures)

^bPaired-sample test was performed to test differences

Buprenorphine buccal film demonstrated a significantly greater decrease in SAO utilization compared to LAO. Starting buprenorphine buccal film treatment led to greater decreases in the number of SAO prescriptions per patient (0.9 vs. 0.3, p < 0.001), mean SAO treatment duration (15.4 vs. 2.2 days, p < 0.001), and average SAO daily doses (9.7 vs. 6.1 MME, p = 0.015). In contrast, the between-cohort comparison of non-opioid rescue medication utilization trends showed a similar impact of buprenorphine buccal film and LAO initiation on prescribing patterns (p = 0.589). A between-group comparison of SAO and non-opioid rescue medication use trends is presented in Table 9.

Table 9.

Between-group comparison of rescue medications utilization changes (6-month follow-up period vs. 6-month pre-index period) in matched patients

	BBF (N = 964)	LAO (N = 964)	P valuea
Non-opioid rescue medications (NORM)
Mean difference in number of NORM prescriptions	− 0.1	− 0.2	0.589
Short-acting opioids (SAO)
Mean difference in SAO treatment duration (days)	− 15.4	− 2.2	< 0.001
Mean difference in number of SAO prescriptions	− 0.9	− 0.3	< 0.001
Mean difference in SAO daily dose (MME)	− 9.7	− 6.1	0.015

BBF buprenorphine buccal film, LAO long-acting opioids, NORM non-opioid rescue medications, SAO short-acting opioids, MME morphine milligram equivalents

^aIndependent t test was performed to test the difference. The P values were validated with mixed repeated-measure ANOVA

Discussion

This retrospective study among the commercially insured US population comprehensively evaluated economic outcomes and treatment characteristics of buprenorphine buccal film and LAO among patients with cLBP previously treated with SAO. The study generally demonstrated similar any-cause and cLBP-related healthcare expenditures in buprenorphine buccal film- and LAO-treated patients during the 12-month follow-up period. Only prescription costs were higher for buprenorphine buccal film (around $2000 per patient), but this was expected since it is a branded medication, while the LAO cohort mainly included generics. Despite these results, the comparison of total costs between the study cohorts lacked statistical significance. On the other hand, healthcare resource utilization was more favorable in buprenorphine buccal film-treated patients. Buprenorphine buccal film had fewer patients with any-cause ED visits and cLBP-related hospitalizations. The average number of any-cause outpatient visits, any-cause hospitalizations, and cLBP-related hospitalizations, as well as the mean duration of cLBP-related hospital stays, was also significantly lower in the buprenorphine buccal film cohort. Regarding treatment characteristics, similar index treatment durations and adherence measures were observed between the cohorts. The mean daily dose was 598.1 mcg for buprenorphine buccal film-treated patients and 47.4 MME per day for LAO-treated patients on average. Most patients used opioid and non-opioid rescue medications concomitantly with index medications during the follow-up period. LAO-treated patients used SAO more frequently, while buprenorphine buccal film-treated patients had higher utilization of the buprenorphine patch and duloxetine. Other non-opioid rescue medications were prescribed similarly in both study cohorts. The trends analysis investigated how transitioning to buprenorphine buccal film or LAO affected the utilization measures of SAO and non-opioid rescue medications. The results showed decreasing trends of SAO use in both cohorts, with buprenorphine buccal film-treated patients experiencing greater reductions in terms of average SAO daily dose, prescription counts per patient, and mean SAO treatment duration. Meanwhile, trends of non-opioid rescue medication use were stable and similar between the cohorts.

It should be noted that the findings are strictly limited to the commercially insured US patients. According to the most recent statistics published by the CDC [22], approximately 53% of US adults with chronic pain conditions have private insurance. Hence, sensitive populations were not widely covered in this analysis, such as elderly patients commonly insured with Medicare (higher economic and comorbidity burden) and Medicaid patients with socioeconomic barriers (financial instability, systemic biases, limited healthcare access, etc.).

At the time of the study, there was a lack of evidence regarding direct economic burden comparisons between buprenorphine buccal film and LAO in US patients with cLBP. Zah et al. [23] conducted a retrospective US commercial claims analysis that assessed the economic burden of buprenorphine buccal film and buprenorphine patch prescribed among patients with cLBP. Index medication treatment durations were similar between cohorts (150–162 days), but the average buprenorphine buccal film daily dose was twice that of the buprenorphine transdermal patch (502 mcg vs. 236.7 mcg, p < 0.001). Although initiation of buprenorphine buccal film treatment led to a higher increase in prescription costs ($1681 vs. $809, p = 0.014), it was associated with more favorable trends in other areas, including a decrease in any-cause outpatient costs ($438 decrease vs. $1734 increase in patch, p = 0.011) and in total cLBP-related costs ($626 decrease vs. $1337 increase in patch, p = 0.033). Resource utilization in ED settings was also significantly lower in buprenorphine buccal film-treated patients (number of any-cause or cLBP-related ED visits and rates of patients with at least one respective visit) [23]. Landsman-Blumberg et al. [24] explored economic outcomes among patients with chronic non-cancer pain with commercial or Medicare Supplemental insurance treated with only SAO, only LAO, a combination of SAO and LAO, or who switched between the two. The study reported that patients using both SAO and LAO in combination had the highest total costs during the 12-month follow-up ($15,190). In contrast, LAO-treated patients incurred lower costs ($4933) compared to those treated with only SAO ($8604) or those who switched between therapies ($10,470) [24].

There are only a few published studies to the authors’ knowledge that investigate opioid use among buprenorphine buccal film-treated patients with a cLBP diagnosis. Real-world analysis by Stanicic et al. [25] compared buprenorphine buccal film and buprenorphine patch treatment characteristics in a sample of commercially insured patients in the USA with a diagnosis of cLBP. Although this study did not consider previous opioid exposure during the patient selection process, the results showed that 86.6% of patients in the buprenorphine buccal film cohort had opioid prescriptions before initiating treatment (84.2% SAO and 21.2% LAO). Initiation of buprenorphine buccal film treatment was associated with decreasing trends in opioid utilization measures during the follow-up period, such as the number of SAO prescriptions per patient (− 0.7 prescriptions, p < 0.001), number of LAO prescriptions per patient (− 0.4 prescriptions, p < 0.001), number of SAO and LAO opioid prescriptions per patient (− 1.1 prescriptions, p < 0.001), average opioid daily MME (− 12.6 MME, p < 0.001), and mean opioid treatment duration (− 13.4 days, p < 0.001). In addition, these reductions in the buprenorphine buccal film cohort were greater than reductions in the buprenorphine patch cohort, showing greater decreases in concomitant opioid use after initiating buprenorphine buccal film vs. buprenorphine patches [25]. Other types of studies have also evaluated the trends in rescue medication use, including placebo-controlled clinical trials of buprenorphine buccal film in cLBP. The published clinical trials of buprenorphine buccal film all demonstrated a lower proportion of patients using rescue medications over the treatment interval compared to control groups [18, 26]. Hence, findings from our current study align with published evidence, both indicating a decrease in opioid use after starting buprenorphine buccal film treatment in patients with cLBP.

Other published studies have examined buprenorphine buccal film and opioid use among US patients with chronic pain conditions in general. Zimmerman et al. [27] used electronic medical records from a chronic pain management care institution in North Carolina to perform a retrospective analysis among patients switching/transitioning from CII opioids to buprenorphine buccal film. The study assessed opioid daily doses in MME and changes in pain scores to investigate how treatment changes affected opioid utilization and pain reduction. Findings showed that initiating buprenorphine buccal film significantly decreased MME by 85.4% and pain scores remained stable during the follow-up period, with greater improvements observed among those undergoing more aggressive titration strategies [27]. Although we were not able to assess the outcomes related to analgesic effects, the literature suggests that pain management efficacy is maintained while transitioning from oral CII opioids to buprenorphine buccal film, despite lower utilization of CII opioid medications after initiating buprenorphine buccal film treatment.

Strengths and Limitations

This is the first retrospective study to the authors’ knowledge that comprehensively evaluated economic burden and treatment characteristics among commercially insured US patients with cLBP who transitioned from an oral CII SAO to buprenorphine buccal film or oral CII LAO. This real-world analysis was performed among continuously insured patients during the observational period using the most recent US retrospective insurance claims database. The PSM ensured a valid between-group comparison by providing a homogenous pool of patients in both cohorts, diminishing the potential impact of differences in patient characteristics on the study findings.

However, certain study limitations need to be noted when interpreting the study results. The first and main limitation is related to the inherent characteristics of real-world data. This limitation originates from the nature of the insurance claims database and the obstacles to coding systems. The primary purpose of collecting retrospective insurance claims is billing; therefore, errors in data entry and miscoding, duplicate, or negative-cost claims may have appeared. This was handled by performing data cleaning, a precise patient selection process, PSM analysis, and other procedures prior to analyzing the study outcomes. The second limitation was related to a precise identification of cLBP, as the coding system lacks specific descriptors of disease chronicity. Hence, the inclusion criterion of patients having two or more unique low-back pain claims within the 6-month pre-index period was necessary to ensure homogeneity among patients regarding this issue. Third, pre-index and post-index periods in trend analysis were potentially too short to capture the long-term impact of index treatments. However, the durations of both periods had to be equal to provide a reliable comparison of rescue medication utilization changes prior to and after index treatment introduction. Comparing utilization measures between 6-month and 12-month periods would not be relevant. The fourth limitation is regarding the limited generalizability of study findings as this analysis was performed among US patients with commercial insurance, which limits the application to the Medicare and Medicaid populations. Finally, the results were not investigated in specific population subgroups (age, sex, CCI, etc.). Yet, their impact on study findings was minimized by PSM and should be explored among non-matched patients in future research. Future research should also focus on establishing long-term follow-up trends (2 or more years of follow-up) and safety issues associated with prolonged buprenorphine or CII opioid use.

Conclusion

This real-world study retrospectively analyzed US commercial insurance claims of patients with cLBP who were transitioning from an oral CII SAO to buprenorphine buccal film or oral CII LAO. The findings suggest that despite higher prescription costs, buprenorphine buccal film had similar total any-cause and cLBP-related costs compared to LAO, along with lower healthcare resource utilization during the 12-month follow-up. In addition, with a similar treatment duration and adherence to the index medication, buprenorphine buccal film-treated patients had lower SAO utilization, but more commonly used buprenorphine transdermal patches and duloxetine. Additional studies comparing various outcomes between buprenorphine buccal film and LAO in real-world clinical practice are needed.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

uthors (Filip Stanicic, Dimitrije Grbic, and Vladimir Zah) equally contributed to this work (made substantial contributions to the conception, design, acquisition, analysis, and data interpretation, drafted the work or revised it critically for important intellectual content, approved the version to be published, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy of integrity of any part of the work are appropriately investigated and resolved).

Funding

Sponsorship for this study and the Rapid Service Fee were funded by Collegium Pharmaceutical Inc., Stoughton, MA, US.

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available due to a confidentiality agreement between ZRx Outcomes Research Inc. and the data provider.

Declarations

Conflict of Interest

Filip Stanicic, Dimitrije Grbic, and Vladimir Zah are employees of ZRx Outcomes Research Inc. ZRx Outcomes Research Inc. received funding from Collegium Pharmaceutical Inc. for conducting this study. The funding source did not have any direct or indirect impact on study findings.

Ethics/Ethical Approval

The Merative MarketScan^® insurance claims database used for this analysis complies with the Health Insurance Portability and Accountability Act of 1996 (HIPAA), protecting patients’ privacy and ensuring the confidentiality of personal data. Since all data within the abovementioned database are de-identified, approval of the institutional review board or the ethics committee for conducting the research was not required.