Download Patterns of Utilization and Cost of Prostacyclins for Pulmonary

PCV35
Patterns of Utilization and Cost
of Prostacyclins for Pulmonary
Arterial Hypertension
Schneider G1, Rotella P1, Raspa S2, Berger A1, Pruett J2, Murphy B1, Lickert C2, Drake W2
Evidera, Lexington, MA, USA, 2Actelion Pharmaceuticals, Inc., South San Francisco, CA, USA
1
BACKGROUND
RESULTS (CONT'D)
ƒƒ Pulmonary arterial hypertension (PAH) is a chronic, progressive condition characterized by increased pressure
in the pulmonary arteries and elevated pulmonary vascular resistance.1 PAH is a subset of pulmonary
hypertension (PH), representing Group 1 of five diagnostic classifications.2 Prostacyclins and prostacyclin
analogues, also known as prostaglandin I2 (PGI2), are potent vasodilators that may be used to treat PAH
patients with World Health Organization (WHO) functional class II–IV symptoms, depending on the specific
PGI2.3-5 Administration of PGI2 can be either parenteral (P-PGI2), which involves continuous intravenous (IV)
or subcutaneous (SC) infusion, or non-parenteral (NP-PGI2), including inhaled (IH) or oral formulations. While
P-PGI2 is the current standard of therapy for the most severe/advanced PAH, NP-PGI2 enables treatment of
the PGI2 pathway in patients with earlier stages of disease. However, a study of the REVEAL registry found
that P-PGI2 was underutilized among the registry’s terminally ill PAH patients, with only 56% receiving P-PGI2
at the time of PAH-related death, suggesting that therapeutic management of PAH patients in clinical practice
may be inconsistent with treatment guidelines.5
ƒƒ The proportion of PAH patients treated with treprostinil increased between 2010 and 2014 while the
proportions treated with iloprost and epoprostenol decreased (Figure 1).
ƒƒ NP-PGI2 use increased during the study interval (Figure 1).
ƒƒ PGI2 polytherapy became increasingly more common during the study interval (Figure 1).
ƒƒ The increase in non-parenteral PGI2 was triggered by a 2.2-fold increase in non-parenteral treprostinil
between 2010 and 2011 (Figure 1).
ƒƒ Treprostinil and iloprost were more commonly used among patients using other PAH-medication during
the same CY (polytherapy); whereas epoprostenol was more commonly used among patients only using
prostacyclins (monotherapy) (data not shown).
Figure 1. Details of PGI2 Use 2010–2014
OBJECTIVE
100%
70%
90%
70%
Cumulative Percent
METHODS
Source Data
60%
80%
50%
60%
40%
50%
30%
40%
ƒƒ A retrospective observational cohort study was conducted using claims data from Truven® commercial and
Medicare databases, which contain medical and pharmacy claims data for over 15 million persons annually
from health plans throughout the United States. The study period was January 1, 2010 to October 31, 2014.
30%
20%
Supportive PAH-related Therapies: Calcium channel blockers, diuretics, oral anticoagulants, cardiac glycosides,
oxygen. Oxygen is covered as durable medical equipment (DME), not as pharmacotherapy; therefore applicable
procedure codes were used for identification.
PAH Medication-related Costs: Costs (the amount in 2013 US$ eligible for payment under the medical plan)
associated with PAH-related medications and supportive therapies
Sample Selection
ƒƒ Five CY specific cohorts (2010–2014) were constituted of adult patients with evidence of PAH. Patients were
considered to have evidence of PAH in a given CY if they satisfied any one of the following criteria:
—— ≥2 outpatient claims with diagnoses of PAH ≥30 days apart AND ≥1 prescriptions for a PAH-specific
medication;
—— ≥1 inpatient claims with diagnoses of PAH AND ≥1 prescriptions for a PAH-specific medication;
—— ≥1 outpatient claims with diagnoses of PAH AND ≥2 prescriptions for PAH-specific medications;
—— A claim for right heart catheterization (RHC) followed by ≥1 claims with diagnoses of PAH followed by ≥1
prescriptions for a PAH-specific medication; where both the claim for PAH and PAH-specific medication
need to be within 1–60 days of the RHC.
Analysis
Monotherapy (%) (right axis)
Polytherapy (%) (right axis)
2011(n = 1119)
2012 (n = 1105)
2013 (n = 949)
2014 (n = 901)
ƒƒ The increase in NP-PGI2 use (and corresponding decrease in P-PGI2 use) occurred between 2010 and
2011, after which it was stable; and was accompanied by increased polytherapy among non-parenteral users
and coinciding decreased monotherapy among parenteral users (Figure 2).
Figure 2. P-PGI2 and NP-PGI2 Use, by Year
60%
PAH-related procedure: The presence of any procedural code identified as being PAH-related (e.g. heart
catheterization, atrial septectomy or septostomy, lung transplant, etc.)
NP-PGI2 (% ) (right axis)
Calendar Year Cohort
Polytherapy: Received PGI2 + other PAH-specific medication during the same CY. Note: polytherapy does not
necessarily imply concomitant medication use, i.e. 2 medications could have been administered at different times
during the same CY.
50%
Cumulative Percent
PAH-related encounter: A medical encounter for which a PAH Diagnosis (ICD-9-CM 416.0 or 416.8) was
present on any claim in any position (i.e. as the primary or non-primary diagnosis) during the encounter.
P-PGI2 (%) (right axis)
Abbreviations: NP-PGI2, non-parenteral prostacyclin; P-PGI2, parenteral prostacyclin
Note: the total of treprostinil + iloprost + epoprostenol in Figure 1 exceeds 100% in each CY as these treatments were not mutually
exclusive.
70%
NP-PGI2: IH or oral administered PGI2 (IH iloprost, IH treprostinil, oral treprostinil)
Epoprostenol, any (left axis)
0%
2010 (n = 905)
Monotherapy: Received only PGI2 and no other PAH-specific medications during calendar year (CY).
P-PGI2: IV epoprostenol (branded/generic/for injection), IV treprostinil, SC treprostinil
Iloprost (left axis)
10%
10%
0%
PAH-specific Medications: PGI2 (epoprostenol, iloprost, treprostinil), endothelin receptor antagonists (ERA;
bosentan, ambrisentan, macitentan), PAH-specific phosphodiesterase type 5 inhibitors (PDE-5i; branded/generic
sildenafil, tadalafil), and soluble guanylate cyclase stimulators (sGCs; riociguat).
Treprostinil, P-PGI2 (left axis)
20%
Study Definitions
PAH Diagnosis: International Classification of Diseases - 9th Revision - Clinical Modification (ICD-9-CM) 416.0
(“Primary pulmonary hypertension”) or 416.8 (“Other chronic pulmonary heart diseases”)
Treprostinil, NP-PGI2 (left axis)
Percent with Characteristic
ƒƒ The primary objective of this research is to estimate annual PAH healthcare utilization and medication related
costs among PAH patients receiving P-PGI2 or NP-PGI2 treatment.
40%
NP-PGI2, Polytherapy
NP-PGI2, Monotherapy
30%
P-PGI2, Polytherapy
P-PGI2, Monotherapy
20%
10%
0%
2010
(n=905)
2011
(n=1119)
2012
(n=1105)
Calendar Year Cohort
2013
(n=949)
2014
(n=901)
Abbreviations: NP-PGI2, non-parenteral prostacyclin; P-PGI2, parenteral prostacyclin
ƒƒ Nominal increases in the year-to-year use of ERAs and PDE-5is were observed (Table 3).
ƒƒ Use of other PAH medications was more common among NP-PGI2 users (Table 3).
Table 3. PAH-specific Medication Characteristics of Patients Using PGI2*
2010
(n = 905)
2011
(n = 1,119)
2012
(n = 1,105)
ERA
385 (42.5%)
493 (44.1%)
483 (43.7%)
436 (45.9%) 424 (47.1%)
PDE-5i
423 (46.7%)
562 (50.2%)
596 (53.9%)
534 (56.3%) 505 (56.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
562 (62.1%)
733 (65.5%)
737 (66.7%)
sGCs
Any of the above 3 categories (i.e., ERA,
PDE-5, sGCs)
2013
(n = 949)
12 (1.3%)
2014
(n = 901)
30 (3.3%)
653 (68.8%) 620 (68.8%)
% using other PAH medications
ƒƒ The prevalence of PAH-specific medications was calculated using all adult PAH patients as the denominator.
All other analyses focused on only PGI2 patients.
ƒƒ Demographics, clinical characteristics, healthcare utilization, and PGI2 costs of patients receiving PGI2 were
assessed separately within each annual cohort.
ƒƒ Costs are annualized at the population level to account for differences in available person-time within each CY
(i.e. annualized costs = costs ÷ months of study enrollment during CY * 12]). However, since PGI2 users did
not necessarily utilize PGI2 for the entirety of their enrollment in a CY, presented costs do not reflect the cost of
a full year of therapy for an individual patient.
ƒƒ Claims-based algorithms were used to identify comorbidities in accordance to the Deyo version of the Charlson
Comorbidity Index (CCI).
Among P-PGI2 users
54.4%
58.6%
60.4%
64.3%
61.2%
Among NP-PGI2 users
75.2%
74.1%
75.0%
75.0%
77.6%
Abbreviations: ERA, endothelin receptor antagonists; NP-PGI2, non-parenteral prostacyclin; PAH, pulmonary arterial hypertension; PDE5i, phosphodiesterase type-5 inhibitor; P-PGI2, parenteral prostacyclin; sGCs, soluble guanylate cyclase stimulators
*Although the denominator used was all prostacyclin patients, by definition only polytherapy patients received PAH-specific medications
other than prostacyclins
ƒƒ Mean (standard deviation [SD]) annualized, PAH-population-based PGI2 costs ranged from $99,919
($100,139) to $118,861 ($136,493) per CY (Figure 3).
ƒƒ The proportion of PAH, population-based, medication related costs attributable to NP-PGI2 treatment
increased on a year-to-year basis (Figure 3).
ƒƒ In CY2010 annualized, PAH-population-based P-PGI2 costs were twice those of NP-PGI2 costs ($69,684 vs.
$34,005), by CY2014, P-PGI2 costs were 8% lower than NP-PGI2 costs ($47,871 vs. $52,047) (Figure 3).
ƒƒ PGI2 was used consistently among PAH patients from year to year, at approximately 21% annually. From
2010–2014, a total of 2,670 PAH patients using PGI2s were identified, with approximately 900 to 1,100 patients
represented in each CY (Table 1).
Figure 3. PAH Medication-related Costs* (% of Total and Dollar Amount) All
PGI2 Users
90%
Table 1. Prevalence of PAH-specific Medications*
Patients aged ≥18 years
4,298
with evidence of PAH
PAH patients using
905 (21.1%)
PGI2
PAH patients using an
2,019 (47.0%)
ERA
2,826 (65.8%)
2011
5,166
1,119 (21.7%)
2,318 (44.9%)
2012
5,299
1,105 (20.9%)
$175,000
80%
2013
4,698
949 (20.2%)
2014
4,310
2010–2014
12,306
901 (20.9%) 2,670 (21.7%)
2,300 (43.4%) 1,931 (41.1%) 1,820 (42.2%) 5,113 (41.5%)
Cumulative Percent of
PAH Medication-Related Cost
2010
$200,000
100%
$150,000
70%
$125,000
60%
$100,000
50%
40%
$75,000
30%
$50,000
20%
3,531 (68.4%)
3,793 (71.6%) 3,496 (74.4%) 3,105 (72.0%) 9,078 (73.8%)
Abbreviations: ERA, endothelin receptor antagonists; PAH, pulmonary arterial hypertension; PDE-5i, phosphodiesterase type 5 inhibitor;
PGI2, prostacyclin
*As calendar year cohorts were not mutually exclusive patients could contribute to >1 CY.
ƒƒ The average age was approximately 56 years, while nearly three-quarters of PAH patients were female (Table
2).
ƒƒ Notwithstanding 2014, comorbidity profiles (as measured by the CCI) and patients with at least a single office
visit varied little year-to-year (Table 2).
ƒƒ The data suggest an apparent decrease in inpatient and emergency room (ER) visits during study timeframe;
particularly PAH-related ER after 2010 (Table 2).
ƒƒ The patient and clinical characteristics presented for the overall PGI2 sample (Table 2) did not differ noticeably
when stratified by mono- and poly- therapy (data not shown).
Table 2.Patient and Clinical Characteristics of PAH Patients Using PGI2
Age in years, Mean (SD)
2010
(n = 905)
55.0 (14.0)
2011
(n = 1,119)
56.8 (13.9)
2012
(n = 1,105)
56.3 (13.9)
2013
(n = 949)
56.4 (14.2)
2014*
(n = 901)
56.8 (14.4)
Gender, n (%) female
684 (75.6%)
805 (71.9%)
815 (73.8%)
719 (75.8%)
682 (75.7%)
10.8 (2.8)
10.9 (2.5)
10.8 (2.7)
8.6 (2.1)
790 (70.6%)
3.0 (2.2)
788 (71.3%)
3.0 (2.2)
669 (70.5%)
3.1 (2.3)
612 (67.9%)
2.8 (2.1)
Months of study enrollment in CY, Mean (SD) 10.7 (2.7)
Payer type, n (%) commercial claims
694 (76.7%)
Charlson Comorbidity Index, Mean (SD)
3.0 (2.2)
Patients with inpatient admission
0%
PDE-5i
Endothelin receptor antagonists (ERA)
NP-PGI2, any
P-PGI2, any
Total PAH-related medication cost (right axis)
Total prostacyclin cost (right axis)
2011 (n = 1119)
2012 (n = 1105)
Calendar Year Cohort
2013 (n = 949)
2014 (n = 901)
LIMITATIONS
ƒƒ There is no ICD-9-CM code specific to PAH, therefore misclassification of our target patient is possible. To
limit this possibility we used algorithms incorporating ICD-9-CM diagnostic codes for PH in combination with
PAH-specific medications and RHC. This study was observational and descriptive in nature, which limits the
ability to make conclusions regarding causality.
CONCLUSION
ƒƒ The results of this study suggest that the overall use of PGI2 among PAH patients was constant during
the five-year study interval (2010–2014), though changes to some specific PGI2 utilization patterns were
observed over this time. Among PGI2 users, there were upward trends for polytherapy (i.e., the use of other
PAH-specific medications in the same year) vs. monotherapy and for the proportion of costs attributable to
NP-PGI2 vs. P-PGI2 throughout the study period. The data also illustrate a specific shift from 2010–2011,
during which time the use of NP-PGI2 rose and PAH-related inpatient stays and ER visits decreased;
those changes persisted through the end of the study period. Further research is needed to determine the
clinical implications of the observed shifts in PGI2 usage, including whether they reflect earlier treatment
during PAH disease progression or are associated with improved outcomes such as decreases in severe
PAH-related sequelae.
487 (53.8%)
525 (46.9%)
529 (47.9%)
463 (48.8%)
357 (39.6%)
446 (49.3%)
476 (42.5%)
478 (43.3%)
419 (44.2%)
335 (37.2%)
Emergency room visits
Any, n (%)
533 (58.9%)
590 (52.7%)
621 (56.2%)
515 (54.3%)
403 (44.7%)
PAH-related, n (%)
340 (37.6%)
252 (22.5%)
265 (24.0%)
208 (21.9%)
172 (19.1%)
Any, n (%)
898 (99.2%) 1,107 (98.9%) 1,102 (99.7%) 944 (99.5%)
893 (99.1%)
3.
PAH-related, n (%)
874 (96.6%) 1,078 (96.3%) 1,070 (96.8%) 914 (96.3%)
867 (96.2%)
4.
Presented at the ISPOR 18th Annual European Congress • 7–11 November 2015 • Milan, Italy
sGCs
Abbreviations: NP-PGI2, non-parenteral prostacyclin; PAH, pulmonary arterial hypertension; PDE-5i, phosphodiesterase type-5
inhibitor; P-PGI2, parenteral prostacyclin; sGCs, soluble guanylate cyclase stimulators
*Costs are annualized population costs and are therefore interpreted as the mean “per PAH patient cost” among all PAH patients with
any PGI2 use during the CY. They do not reflect the cost of a full year of therapy for an individual patient.
PAH-related, n (%)
Abbreviations: CY, calendar year; PAH, pulmonary arterial hypertension; PH, pulmonary hypertension; SD, standard deviation
*Months of enrollment less in 2014 as data was available only through October of that year, this impacts accumulation of events in 2014,
particularly inpatient and ER visits
Supportive PAH-related Therapies
$0
2010 (n = 905)
Any, n (%)
Office visits
$25,000
10%
Total Amount (US$) of Medication Costs
RESULTS
PAH patients using a
PDE-5i
80%
110%
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Disclosures: This study was sponsored by Actelion Pharmaceuticals US, Inc. Data collection
and analysis were conducted by Evidera and funded by Actelion Pharmaceuticals Ltd.
Authors GS, PR, AB, and BM are full-time employees of Evidera.
Authors SR, JP, CL, and WD are employees of Actelion Pharmaceuticals US.