Association Between Copayment and Adherence to Medications for Pulmonary Arterial Hypertension.

Background Pharmacologic treatment for pulmonary arterial hypertension (PAH) improves exercise capacity, functional class, and hemodynamic indexes. However, monthly prescription costs often exceed $4000. We examined associations between (1) medication copayment and (2) annual household income with adherence to pulmonary vasodilator therapy among individuals with PAH. Methods and Results We used administrative claims data from an insured population in the United States to identify individuals diagnosed with PAH between 2015 and 2020. All individuals had ≥1 medication claim for endothelin receptor antagonists, phosphodiesterase type-5 inhibitors, prostanoids or prostacyclin receptor agonists, or the soluble guanylate cyclase stimulator riociguat. We defined copayments as low, medium, or high, as determined by their distributions for each medication class. Annual household income was categorized as <$40 000, $40 000 to $74 999, and ≥$75 000. The primary outcome was medication adherence, defined by proportion of days covered ≥80%. We studied 4025 adults (aged 65.9±13.3 years; 71.2% women). Compared with those with annual household income ≥$75 000, individuals in the <$40 000 and $40 000 to $74 999 categories had no significant differences in medication adherence. Compared with those with low copayments, individuals with high copayments had decreased adherence to prostanoids (odds ratio [OR], 0.36 [95% CI, 0.20-0.65]; P<0.001) and combination therapy with endothelin receptor antagonist and phosphodiesterase type-5 inhibitor (OR, 0.61 [95% CI, 0.38-0.97]; P=0.03). Conclusions We identified associations between copayment and adherence to prostanoids and combination therapy among individuals with PAH. Copayment may be a structural barrier to medication adherence and merits inclusion in studies examining access to pharmacotherapy among individuals with PAH.

Cost-Effectiveness of Combination Therapy for Patients With Systemic Sclerosis-Related Pulmonary Arterial Hypertension.

Background To evaluate the cost-effectiveness of combination pulmonary arterial hypertension specific therapy in systemic sclerosis-related PAH. Methods and Results Health outcomes and costs were captured through data linkage. Health utility was derived from Medical Outcomes Study Short Form-36 scores. A probabilistic discrete-time model was developed to simulate lifetime changes in costs and health utility. Mortality was predicted using a Gompertz parametric survival model. For both treatment arms, the simulations were started using the same cohort of 10 000 patients. Probabilistic sensitivity analysis was performed using the Monte Carlo simulation with 1000 sets of sampled parameter values. Of 143 patients with systemic sclerosis-related pulmonary arterial hypertension, 89 were on monotherapy and 54 on combination therapy. Mean simulated costs per patient per year in monotherapy and combination therapy groups were AU$23 411 (US$16 080) and AU$29 129 (US$19 982), respectively. Mean life years and quality-adjusted life years from pulmonary arterial hypertension diagnosis to death of patients receiving monotherapy were 7.1 and 3.0, respectively, and of those receiving combination therapy were 9.2 and 3.9, respectively. Incremental costs per life year and quality-adjusted life year gained of combination therapy compared with monotherapy were AU$47 989 (US$32 920) and AU$113 823 (US$78 082), respectively. At a willingness-to-pay threshold of AU$102 000 (US$69 972) per life year gained, and of AU$177 222 (US$121 574) per quality-adjusted life year gained, the probability of combination therapy being cost-effective was 0.95. Conclusions The incremental cost per quality-adjusted life year gained of combination therapy compared with monotherapy was substantial in the base case analysis. Given the fatal prognosis of systemic sclerosis-related pulmonary arterial hypertension and the incremental cost per life year of AU$47 989 (US$32 920), combination therapy could be considered cost-effective in systemic sclerosis-related pulmonary arterial hypertension.

Burden of pulmonary arterial hypertension in England: retrospective HES database analysis.

BACKGROUND: The clinical and economic burden of pulmonary arterial hypertension (PAH) is poorly understood outside the United States. This retrospective database study describes the characteristics of patients with PAH in England, including their healthcare resource utilisation (HCRU) and associated costs. METHODS: Data from 1 April 2012 to 31 March 2018 were obtained from the National Health Service (NHS) Digital Hospital Episode Statistics database, which provides full coverage of patient events occurring in NHS England hospitals. An adult patient cohort was defined using an algorithm incorporating pulmonary hypertension (PH) diagnosis codes, PAH-associated procedures, PH specialist centre visits and PAH-specific medications. HCRU included inpatient admissions, outpatient visits and Accident and Emergency (A&E) attendances. Associated costs, calculated using national tariffs inflation-adjusted to 2017, did not include PAH-specific drugs on the High Cost Drugs list. RESULTS: The analysis cohort included 2527 patients (68.4% female; 63.6% aged ⩾50 years). Mean annual HCRU rates ranged from 2.9 to 3.2 for admissions (21-25% of patients had ⩾5 admissions), 9.4-10.3 for outpatient visits and 0.8-0.9 for A&E attendances. Costs from 2013 to 2017 totalled £43.2M (£33.9M admissions, £8.3M outpatient visits and £0.9M A&E attendances). From 2013 to 2017, mean cost per patient decreased 13% (from £4400 to £3833) for admissions and 13% (from £1031 to £896) for outpatient visits, but increased 52% (from £81 to £123) for A&E attendances. CONCLUSION: PAH incurs a heavy economic burden on a per-patient basis, highlighting the need for improved treatment strategies able to reduce disease progression and hospitalisations.The reviews of this paper are available via the supplemental material section.

Prevalence of pulmonary arterial hypertension in the Camerino area of central Italy and savings resulting from generic bosentan.

Objective: Pulmonary arterial hypertension is a rare and progressive respiratory disease characterised by high blood pressure and vascular resistance producing right ventricular fatigue. In Italy, pulmonary hypertension can be treated with different drugs available on the market at different costs, and in the Marche region distributed exclusively by hospital pharmacies. The present study examined in an area of the Marche region the use of drugs specifically indicated for pulmonary hypertension, and evaluated how the introduction of the generic bosentan might lower pharmaceutical costs for the healthcare budget. Methods: The study examined oral administration prescriptions and costs using data from the Apotheke Gold (Record Data) database from 1 January 2012 to 31 August 2017. Results: Annually (from 1 January 2012 to 31 August 2017), an average of 4.83 patients were treated (prevalence of 102.35 cases per 1 million residents) with ambrisentan (Volibris), bosentan (Tracleer), macitentan (Opsumit), tadalafil (Adcirca) or sildenafil (Revatio). The total expenditure during the 5-year 8-month period was €472 405. Ambrisentan was by far the most expensive product overall, with a total expenditure of €222 380 for the period studied (a daily cost of €67.39), even though Tracleer had the highest cost for a day of treatment (a daily cost of €94.48, but a total expenditure of €163 976 for the period, due to its more recent marketing). Providing patients with the generic form bosentan in place of Tracleer would lower the costs dramatically. A very significant annual savings per patient of approximately €31 879 would be achieved, a striking 92.4% reduction in costs. Conclusion: The prevalence of pulmonary arterial hypertension reported for Camerino and its surrounding area in the Marches region is quite high compared with that reported by other authors for France and Scotland. The introduction of the generic bosentan would cut costs drastically. It is to be hoped that centralised procurement at the regional level would bring further savings.

The economic burden of systemic sclerosis related pulmonary arterial hypertension in Australia.

BACKGROUND: To quantify the financial cost of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc). METHODS: Healthcare use was captured through data linkage, wherein clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with hospital, emergency department (ED) and ambulatory care databases (MBS) for the period 2008-2015. PAH was diagnosed on right heart catheter according to international criteria. Determinants of healthcare cost were estimated using logistic regression. RESULTS: Total median (25th-75th) healthcare cost per patient (including hospital, ED and MBS cost but excluding medication cost) for our cohort during 2008-2015 was AUD$37,685 (18,144-78,811) with an annual per patient healthcare cost of AUD$7506 (5273-10,654). Total healthcare cost was higher for SSc-PAH patients compared with those without PAH with a total cost per patient of AUD$70,034 (37,222-110,814) vs AUD$34,325 (16,093 - 69,957), p < 0.001 respectively with an annual excess healthcare cost per PAH patient of AUD$2463 (1973-1885), p < 0.001. The cost of SSc-PAH occurs early post PAH diagnosis with 89.4% utilizing a healthcare service within the first 12 months post PAH diagnosis with an associated cost per patient of AUD$4125 (0-15,666). PAH severity was the main significant determinant of increased healthcare cost (OR 2.5, p = 0.03) in our PAH cohort. CONCLUSIONS: Despite SSc-PAH being a low prevalence disease, it is associated with significant healthcare resource utilization and associated economic burden, predominantly driven by the severity of PAH.

Hospital burden of pulmonary arterial hypertension in France.

BACKGROUND & AIMS: Pulmonary arterial hypertension is a severe disease associated with frequent hospitalisations. This retrospective analysis of the French medical information PMSI-MSO database aimed to describe incident cases of patients with pulmonary arterial hypertension hospitalised in France in 2013 and to document associated hospitalisation costs from the national health insurance perspective. METHODS: Cases of pulmonary arterial hypertension were identified using a diagnostic algorithm. All cases hospitalised in 2013 with no hospitalisation the previous two years were retained. All hospital stays during the year following the index hospitalisation were extracted, and classified as incident stays, monitoring stays or stays due to disease worsening. Costs were attributed from French national tariffs. RESULTS: 384 patients in France were hospitalised with incident pulmonary arterial hypertension in 2013. Over the following twelve months, patients made 1,271 stays related to pulmonary arterial hypertension (415 incident stays, 604 monitoring stays and 252 worsening stays). Mean age was 59.6 years and 241 (62.8%) patients were women. Liver disease and connective tissue diseases were documented in 62 patients (16.1%) each. Thirty-one patients (8.1%) died during hospitalisation and four (1.0%) received a lung/heart-lung transplantation. The total annual cost of these hospitalisations was € 3,640,382. € 2,985,936 was attributable to standard tariffs (82.0%), € 463,325 to additional ICU stays (12.7%) and € 191,118 to expensive drugs (5.2%). The mean cost/stay was € 2,864, ranging from € 1,282 for monitoring stays to € 7,285 for worsening stays. CONCLUSIONS: Although pulmonary arterial hypertension is rare, it carries a high economic burden.

Cost savings with a novel algorithm for early detection of systemic sclerosis-related pulmonary arterial hypertension: alternative scenario analyses.

Pulmonary arterial hypertension is an important cause of death and disability in patients with systemic sclerosis (SSc). Yearly screening of all SSc patients with transthoracic echocardiography (TTE) is recommended in international guidelines and currently utilised by the Australian Scleroderma Interest Group (ASIGSTANDARD ). Owing to the limitations of TTE, the ASIG developed a new screening algorithm (ASIGPROPOSED ) utilising a serum biomarker, NT-proBNP, in place of TTE, which has been shown to be equally accurate as the current algorithm. The aim of this study was to compare the cost of these two algorithms using different scenarios. The new algorithm resulted in significant yearly cost savings of between AU$42 913.35 and AU$84 570 in screening and diagnosis of an Australian cohort which, if extrapolated to the Australian population, would result in a yearly cost saving of between AU$367 066 and AU$725 564. There was no scenario in which the proposed algorithm did not result in a cost saving.

High rates of medication adherence in patients with pulmonary arterial hypertension: An integrated specialty pharmacy approach.

Phosphodiesterase-5 inhibitors (PDE-5I) have demonstrated improvement in disease symptoms and quality of life for patients with pulmonary arterial hypertension (PAH). Despite these benefits, reported adherence to PDE-5I therapy is sub-optimal. Clinical pharmacists at an integrated practice site are in a unique position to mitigate barriers related to PAH therapy including medication adherence and costs. The primary objective of this study was to assess medication adherence to PDE-5I therapy within an integrated care model at an academic institution. The secondary objective was to assess the impact of out-of-pocket (OOP) cost, frequency of dosing, adverse events (AE) and PAH-related hospitalizations on medication adherence. We performed a retrospective cohort analysis of adult patients with PAH who were prescribed PDE-5I therapy by the center's outpatient pulmonary clinic and who received medication management through the center's specialty pharmacy. We defined optimal medication adherence as proportion of days covered (PDC) ≥ 80%. Clinical data including AEs and PAH-related hospitalizations were extracted from the electronic medical record, and financial data from pharmacy claims. Of the 131 patients meeting inclusion criteria, 94% achieved optimal adherence of ≥ 80% PDC. In this study population, 47% of patients experienced an AE and 27% had at least one hospitalization. The median monthly OOP cost was $0.62. Patients with PDC<80% were more likely to report an AE compared to patients with PDC≥ 80% (p = 0.002). Hospitalization, OOP cost, and frequency of dosing were not associated with adherence in this cohort. Patients receiving PDE-5I therapy through an integrated model achieved high adherence rates and low OOP costs.

Identifying Patients with Pulmonary Arterial Hypertension Using Administrative Claims Algorithms.

Retrospective administrative claims database studies provide real-world evidence about treatment patterns, healthcare resource use, and costs for patients and are increasingly used to inform policy-making, drug formulary, and regulatory decisions. However, there is no standard methodology to identify patients with pulmonary arterial hypertension (PAH) from administrative claims data. Given the number of approved drugs now available for patients with PAH, the cost of PAH treatments, and the significant healthcare resource use associated with the care of patients with PAH, there is a considerable need to develop an evidence-based and systematic approach to accurately identify these patients in claims databases. A panel of pulmonary hypertension clinical experts and researchers experienced in retrospective claims database studies convened to review relevant literature and recommend best practices for developing algorithms to identify patients with PAH in administrative claims databases specific to a particular research hypothesis.

Clinical trial design and new therapies for pulmonary arterial hypertension.

Until 20 years ago the treatment of pulmonary arterial hypertension (PAH) was based on case reports and small series, and was largely ineffectual. As a deeper understanding of the pathogenesis and pathophysiology of PAH evolved over the subsequent two decades, coupled with epidemiological studies defining the clinical and demographic characteristics of the condition, a renewed interest in treatment development emerged through collaborations between international experts, industry and regulatory agencies. These efforts led to the performance of robust, high-quality clinical trials of novel therapies that targeted putative pathogenic pathways, leading to the approval of more than 10 novel therapies that have beneficially impacted both the quality and duration of life. However, our understanding of PAH remains incomplete and there is no cure. Accordingly, efforts are now focused on identifying novel pathogenic pathways that may be targeted, and applying more rigorous clinical trial designs to better define the efficacy of these new potential treatments and their role in the management scheme. This article, prepared by a Task Force comprised of expert clinicians, trialists and regulators, summarises the current state of the art, and provides insight into the opportunities and challenges for identifying and assessing the efficacy and safety of new treatments for this challenging condition.