A total of 405 patients initiated oral treprostinil or selexipag during the study period. After applying study criteria, 256 patients with PAH (130 receiving oral treprostinil; 126 receiving selexipag) met the study criteria. Table 1 provides a description of the baseline demographic and clinical characteristics of the study cohort. Oral treprostinil and selexipag patients were of similar age (mean 58.0 ± 16.2 vs. 58.5 ± 13.0 years for oral treprostinil and selexipag, respectively) and had a similar Charlson Comorbidity Index (mean 3.5 ± 2.6 vs. 3.2 ± 2.2 for oral treprostinil and selexipag, respectively). The proportion of males was higher in the oral treprostinil cohort (33.1 vs. 16.7% for oral treprostinil and selexipag, respectively; p < 0.01). Rates of specific comorbidities varied, with more rheumatic disease in the selexipag cohort (20 vs. 32.5% for oral treprostinil and selexipag, respectively; p = 0.023) and a nonsignificant trend toward more renal disease and AIDS/HIV in the oral treprostinil cohort. There was a 10% difference in the proportion of patients who underwent RHC in the 6 months prior to being prescribed oral prostacyclin, although this difference did not meet statistical significance (47.7 vs. 36.5% for oral treprostinil and selexipag, respectively; p = 0.07).
Table 1 Baseline demographic, clinical characteristics, treatments, and costs Baseline treatment patterns were compared between the cohorts (Table 1). A higher proportion of patients in the selexipag cohort used a PDE-5i alone or in combination with an ERA (73.8 vs. 66.2% for selexipag and oral treprostinil, respectively; p = 0.18) during baseline, although this difference was not statistically significant. More patients receiving oral treprostinil transitioned from a parenteral prostacyclin (14.6 vs. 4.0% for oral treprostinil and selexipag, respectively; p = 0.004).
Baseline total all-cause costs were similar between the cohorts except for all-cause outpatient costs, which were higher in the oral treprostinil cohort than in the selexipag cohort (mean $23,883 ± 88,718 and $11,600 ± 17,450, respectively; p = 0.025) (Table 1). Mean baseline PAH-related medical and pharmacy costs were similar across the cohorts, as were PAH-related total healthcare costs.
Adherence and Persistence
Following the initiation of oral prostacyclin therapy, the mean MPR was higher for oral treprostinil than for selexipag (0.89 ± 0.19 vs. 0.85 ± 0.22, respectively; p = 0.039). While the proportion of patients with MPR ≥ 80 was higher in the oral treprostinil cohort (82%) than in the selexipag cohort (77%), this difference was not statistically significant (Fig. 2). Mean PDC was similar between the cohorts (0.72 ± 0.31 vs. 0.71 ± 0.31 for oral treprostinil and selexipag, respectively; p = 0.483), and the proportion of patients with PDC ≥ 80 was the same in both cohorts (56%; p = 0.975). There was no significant difference between the cohorts in the proportion of patients persistent on therapy when discontinuation was defined as a gap of ≥ 60 days (71 vs. 72% for oral treprostinil and selexipag, respectively; p = 0.797) or a gap of ≥ 30 days (62 vs. 63%, respectively; p = 0.797).
Prescriptions and Monthly Dosing
The mean number of prescriptions was 6.1 ± 3.3 and 5.8 ± 2.7 for oral treprostinil and selexipag, respectively, which did not differ between cohorts (p = 0.310). Similarly, the median and interquartile range (IQR) for the number of prescriptions was 6.5 (4–7) and 6 (5–7) for oral treprostinil and selexipag, respectively.
In prostacyclin-naïve patients, the median total daily dose at 6 months was 6.9 mg (IQR 2.2–9.5) for oral treprostinil and 2213 μg (IQR 1200–3093) for selexipag. Median total daily dose generally increased from month 1 through 6. In sensitivity analysis over 12 months post-index, daily median doses generally reached their highest point in month 6 and did not fluctuate much from 6 through 12 months.
In patients who received parenteral prostacyclin before initiation of oral prostacyclin, median total daily doses started higher, as expected, but also remained higher over 6-month follow-up than in those who were prostacyclin naïve. Among patients who received prior parenteral prostacyclin-class therapies, the median total daily dose at 6 months was 11.8 mg (IQR 4.4–20.4) for oral treprostinil and 2600 μg (IQR 1365–3200) for selexipag. In a sensitivity analysis over the 12-month post-index period among these patients, median total daily doses reached their highest points between months 6 and 12 for both cohorts, generally later than for those who were prostacyclin naïve at the time of oral prostacyclin initiation.
Healthcare Resource Use and Costs
There was no significant difference between the cohorts in all-cause inpatient visits (Table 2) during the post-index period. The adjusted mean number of inpatient visits was 1.3 ± 0.6 for the oral treprostinil cohort and 1.9 ± 0.8 for the selexipag cohort (p = 0.199). Adjusted mean length of hospital stay was 8.6 ± 6.1 days for the oral treprostinil cohort and 10.4 ± 7.3 days for the selexipag cohort (p = 0.441). Similarly, the mean number of all-cause emergency department (ED) visits was similar (0.4 ± 1.1 and 0.4 ± 1.0 for oral treprostinil and selexipag, respectively; p = 0.917). However, the mean all-cause adjusted outpatient visits was higher in the oral treprostinil cohort (22.0 ± 8.4 vs. 18.8 ± 7.2 for oral treprostinil and selexipag, respectively; p < 0.001).
Table 2 Healthcare resource utilization during the post-index period There was no significant difference between the two cohorts for PAH-related medical utilization (inpatient visits, ED visits, and outpatient visits) or the number of unique PAH-related prescriptions (Table 2). The mean number of all-cause unique prescriptions was similar between the cohorts (45 ± 20 vs. 49 ± 22 for oral treprostinil and selexipag, respectively; p = 0.121). Notably, a higher proportion of patients in the oral treprostinil cohort received RHC during the post-index period compared with the selexipag cohort (13.2 vs. 5.6%, respectively; p = 0.039).
All-cause healthcare costs differed between the cohorts (Fig. 3). The mean all-cause total pharmacy cost during the follow-up was higher in the cohort treated with selexipag ($171,169 ± 111,812) than in the cohort treated with oral treprostinil ($118,962 ± 110,675; p < 0.001), and this largely contributed to the difference in total costs ($189,375 ± 114,549) compared with the cohort treated with oral treprostinil ($153,457 ± 159,761; p < 0.001). Similar results were seen when comparing PAH-related total healthcare and pharmacy costs.
A sensitivity analysis was also conducted to explore pharmacy differences among persistent users throughout 6 and 12 months of follow-up (Table 3). Analysis conducted over 6 and 12 months showed that higher pharmacy costs persisted in the selexipag cohort compared with the oral treprostinil cohort. At 6 months, the median pharmacy costs directly attributable to oral treprostinil ($39,392 [IQR 21,483–77,748]) were significantly less than for selexipag ($127,335 [IQR 109,908–136,030]; p < 0.0001). Similarly, median pharmacy costs for persistent users over 12 months directly attributable to oral treprostinil ($125,420 [IQR 60,043–194,605]) were significantly less than for selexipag ($219,250 [IQR 201,624–239,696]; p < 0.0001).
Table 3 Cost of oral treprostinil vs. selexipag among patients persistent on therapy After adjustment for covariates, treatment with oral treprostinil was associated with 51.4% lower total all-cause healthcare costs than treatment with selexipag (difference in mean − $73,680; 95% confidence interval [CI] − 103,702 to − 43,963) (Fig. 4). This difference in all-cause healthcare costs was largely driven by all-cause pharmacy costs, which were 68.2% lower in patients being treated with oral treprostinil than in those being treated with selexipag (difference in mean − $77,654; 95% CI − 105,392 to − 52,118). Treatment with oral treprostinil was associated with 66.9% lower total PAH-related healthcare costs compared with being treated with selexipag (difference in mean − $75,183; 95% CI − 102,584 to − 49,771). Differences in PAH-related healthcare costs were largely driven by PAH-related pharmacy costs, which were 70.62% lower in patients treated with oral treprostinil than in those treated with selexipag (difference in mean − $76,439; 95% CI − 104,512 to − 51,458).