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. 3The alt text for this image may have been generated using AI.

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 PopulationDemographic 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

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 patientsMatched 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 BurdenHealthcare 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 patientsHealthcare 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 patientsTreatment CharacteristicsIndex 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 patientsRescue 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

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 patientsTrends 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

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