Recommendations for the use of oral treprostinil in clinical practice: a Delphi consensus project pulmonary circulation

Abstract

Oral treprostinil was recently labeled for treatment of pulmonary arterial hypertension. Similar to the period immediately after parenteral treprostinil was approved, there is a significant knowledge gap for practicing physicians who might prescribe oral treprostinil. Despite its oral route of delivery, use of the drug is challenging because of the requirement for careful titration and management of drug-related adverse effects. We aimed to create a consensus document combining available evidence with expert opinion to provide guidance for use of oral treprostinil. Following a methodology commonly used in business and social sciences (the ‘Delphi Process’), two investigators from the oral treprostinil (Freedom) studies created a series of statements based on available evidence and the package insert. The set of ‘best practice’ statements was circulated to nine other Freedom trial investigators. Their comments were incorporated into the document as new line items for further vote and comment. The subsequent document was put to vote line by line (scale of −5 to +5) and a final statement was drafted. Consensus recommendations include initial therapy with 0.125 mg for treatment naÿ patients, three times daily dosing, aggressive use of antidiarrheal medication, and a strong preference for use of the drug in combination with other approved PAH therapies. This process was particularly valuable in providing guidance for the management of adverse events (where essentially no data is available). The Delphi process was useful to codify investigator experience and subsequently develop investigator consensus about practical issues for physicians who may wish to prescribe oral treprostinil.

Management of repository corticotrophin injection therapy for pulmonary sarcoidosis: a Delphi study

“…Baughman) have extensive experience organising initial panels of experts and have previous experience conducting Delphi studies that have resulted in publications that are used by physicians in clinical practice. The prior studies produced consensus recommendations for the use of oral treprostinil for pulmonary arterial hypertension [22] and recommendations on the clinical management of pulmonary arterial hypertension patients receiving macitentan [23], in addition to the recommendations on a treatment algorithm for sarcoidosis in this series [13].…”

Comparative effectiveness of oral prostacyclin pathway drugs on hospitalization in patients with pulmonary hypertension in the United States: a retrospective database analysis

“…32,33 A recent Delphi panel on the use of oral treprostinil suggested aggressive antidiarrheal medication to manage these adverse effects, but failed to reach consensus on optimal dosing strategies. 34 In FREEDOM-EV, oral treprostinil was dosed TID; 21 although this could help reduce the intensity of adverse effects to allow increasing the dose to a therapeutic level, 34 TID dosing could introduce adherence issues compared with a drug with less frequent dosing. 35,36 The primary limitation of this study is that whereas the index drugs are indicated solely for specified patients with PAH (not other forms of PH) there is no unique ICD-9-CM or ICD-10-CM code for PAH.…”

Long‐term study of oral treprostinil to treat pulmonary arterial hypertension: dosing, tolerability, and pharmacokinetics

“…Attrition due to AE typical for prostacyclin class medication was ~13% in the initial short-term studies and continued during the open-label extension, but AE may be less intense with a TID dosing strategy. 21…”