Session VI – Looking to the Future

Pharmacoeconomics and Cost Effectiveness of Care in Pulmonary Hypertension

The magnitude of healthcare expenditure in the United States has exponentially increased since the 1980s. Prescription drug expenditures reflect this increase with projected costs of $408 billion by 2019 compared with $255 billion in 2009.

There is a significant difference in costs associated with specialty pharmacy drugs dealing with rare diseases. Costs of pulmonary hypertension medications are among the top 10 expenditures, ranging from annual costs of approximately $22,000 to nearly $200,000. With newer guidelines advocating for combinations therapies of these expensive drugs, costs will increase significantly. There is a need for evidence-based endpoints to justify the cost, including reduction of symptom burden, avoidance of hospitalization, minimization of treatment burden, and improvement in survival.

Medications and hospitalizations account for the most costs in PAH patients. In response, payers are adopting various strategies to minimize costs including restricted drug choices. This has created a need to use these expensive drugs judiciously, beginning with acquiring data on cost-offsets associated with PAH-targeted therapies, including reduced hospitalizations and side effects.

Key Points

• Healthcare costs are significant in PAH.
• Medications represent a significant financial burden for PAH patients and should be considered a primary endpoint of prospective studies.
• Expect increased challenges to justify high-cost therapies.
• Providers need to address payer strategies that target cost containment while continuing to be patient advocates for treatment decisions.

The Next Horizons for Pulmonary Hypertension Treatment

This section looks at the latest innovations in therapies and management strategies for PH.

Monotherapy vs combination therapy
The AMBITION study was the first pivotal study to prove the efficacy of dual combination PAH drug strategy. A pilot study in France has shown remarkable outcomes using combination bosentan, sildenafil, and IV epoprostenol to treat patients with functional class III/IV disease. The TRITON study is currently looking at using three drugs versus two, and the results are expected to favor the three-drug combination.

Upfront vs rapid-sequence therapy
There are no real data favoring either of these strategies over the other. With rapid sequence therapy (ie, adding drugs within 3 months of initiating therapy), the expected adverse effect profile should be more manageable.

Equivalency of drugs
This relates to deciding which drugs to use and in what order. It is a largely understudied topic, and most studies looking at comparing combination drugs were poorly designed with small numbers. Also, they were not designed to test for intra-group equivalency.

New therapies
Many drugs are being investigated for PAH. Some of the most promising drugs are an antioxidant bardoxolone (antioxidant), an oral prostaglandin analog (ralinepag), a leukotriene inhibitor (ubenimex), and IL-6 antagonists.

Newer delivery systems are being developed to improve compliance, including premixed epoprostenol, implantable pump, disposable pumps, and a heart monitoring system that uses implantable sensors for continuous reading of pulmonary pressures.

Stem cell and regenerative therapies, targeted therapies for metabolics, proteins, mRNA transcription, and protein-DNA interactions are being investigated for potential PAH treatment.

Key Points

• Combination therapy, as opposed to monotherapy, is quickly becoming the standard of care.
• There is no evidence supporting upfront combination therapy versus sequential combination therapy, although adverse events can be better managed with sequential therapy.
• Evidence is widely lacking on the equivalency or superiority of PAH medications.
• New therapies for PAH being studied include antioxidants, prostaglandin analogs, leukotriene inhibitors, IL-6 antagonists, newer delivery systems, stem cell regeneration therapies, and other targeted therapies.

Session VI – Looking to the Future References

Pharmacoeconomics and Cost Effectiveness of Care in Pulmonary Hypertension Related References

1. Burger CD, Long PK, Shah MR, et al. Characterization of first-time hospitalizations in patients with newly diagnosed pulmonary arterial hypertension in the REVEAL registry. Chest. 2014;146(5):1263-1273.
2. Galié N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67-119.
3. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425-36.
4. Pulido T, Adzerikho I, Channick RN, et al; SERAPHIN Investigators. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809-18.
5. Taichman DB, Ornelas J, Chung L, et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report. Chest. 2014;146(2):449-75.

The Next Horizons for Pulmonary Hypertension Treatment Related References

1. Ewert R, Richter MJ, Steringer-Mascherbauer R, et al. Intravenous treprostinil infusion via a fully implantable pump for pulmonary arterial hypertension. Clin Res Cardiol. 2017;106(10):776-83.
2. Galiè N1, Barberá JA, Frost AE, et al; AMBITION Investigators. initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373(9):834-44. doi: 10.1056/NEJMoa1413687.
3. McLaughlin V, Channick RN, Ghofrani HA, et al. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur Respir J. 2015;46(2):405-13.
4. Sitbon O, Jaís X, Savale L, et al. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. Eur Respir J. 2014;43(6):1691-7.
5. Walkey AJ, Fein D, Horbowicz KJ, Farber HW. Differential response to intravenous prostacyclin analog therapy in patients with pulmonary arterial hypertension. Pulm Pharmacol Ther. 2011;24(4):421-5.