title: Cost effectiveness of prostacyclins in pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is considered an orphan disease. Prostacyclins are the keystone for PAH treatment. Choosing between the three available prostacyclin therapies could be complicated because there are no comparison studies, so the final decision must be driven by factors such as efficacy, administration route, safety profile and economic aspects.
  
  
  OBJECTIVE
  This study provides a cost-effectiveness and cost-utility comparison of initiating prostacyclin therapy with three different treatment alternatives (inhaled iloprost [ILO], intravenous epoprostenol [EPO] and subcutaneous treprostinil [TRE]) for patients with PAH. The goal of this work is to help physicians with their therapeutic decision-making.
  
  
  METHODS
  A Markov model was built to simulate a patient cohort with class III PAH according to the classification of the New York Heart Association (NYHA). Four health states corresponding with the NYHA classes plus death were allowed for patients in the model. Changing the treatment was possible when patients worsened from functional class III to IV. The time horizon was 3 years, allowing patients to transition between health states on a 12-week cycle basis. The study perspective was that of the National Health System (NHS) [only direct medical costs were included]. Unitary costs were obtained from the Drug Catalogue and e-Salud Database in 2009 and are given in euros (€). Data on health resources and treatment pathways were informed by a four-member expert panel. Efficacy was obtained from pivotal clinical trials of ILO, EPO and TRE, the latter used in Spain as a foreign medication. Utilities for each health state were obtained from the literature. The final efficacy measure was life-years gained (LYG), and utilities were used to obtain quality-adjusted life-years (QALYs). Costs and effects were discounted at a 3% rate. To check for the robustness of the results, sensitivity analyses were performed.
  
  
  RESULTS
  At the end of the 3 years, in the base case of the deterministic analysis, initiating prostacyclin therapy with iloprost was the less costly strategy (€132,840), followed by treprostinil (€359,869) and epoprostenol (€429,775). Epoprostenol has shown the best efficacy results with 2.73 LYG and 1.78 QALY, followed by iloprost (2.69 LYG and 1.74 QALY) and treprostinil (2.69 LYG and 1.73 QALY). Incremental cost-effectiveness ratios (ICER) and cost-utility ratios (ICUR) of epoprostenol versus iloprost and treprostinil were much above the €30,000 per LYG or QALY threshold commonly used in Spain. Iloprost was dominant compared with treprostinil. In the probabilistic analysis, epoprostenol, when compared with iloprost, was a dominant strategy in 15% of the simulations, but it was not a cost-effective option in 83% of the cases. When compared with treprostinil, epoprostenol was dominant in 43% of the simulations. Iloprost was dominant compared with treprostinil in 45% of the cases and it was a cost-effective alternative in 39% of the simulations.
  
  
  CONCLUSIONS
  Initiating prostacyclin treatment with iloprost in patients with PAH, functional class III of the NYHA, is the less costly alternative for the NHS in Spain, with a good efficacy profile when compared with the other alternatives.
authors.affiliation: Department of Pneumology, Hospital Universitari Vall dHebron, CIBERES, Barcelona, Catalonia, Spain. aroman@vhebron.net
authors.forename: Antonio
authors.initials: A
authors.lastname: Roman
authors.forename: Joan A
authors.initials: JA
authors.lastname: Barberà
authors.forename: Pilar
authors.initials: P
authors.lastname: Escribano
authors.forename: Maria L
authors.initials: ML
authors.lastname: Sala
authors.forename: Laia
authors.initials: L
authors.lastname: Febrer
authors.forename: Itziar
authors.initials: I
authors.lastname: Oyagüez
authors.forename: Eliazar
authors.initials: E
authors.lastname: Sabater
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Casado
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000191:economics / Q000494:pharmacology; D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000191:economics* / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000191:economics*; D016285:Iloprost / Q000191:economics* / Q000627:therapeutic use; D008390:Markov Chains; D018803:Models, Economic; D044062:Prostaglandins I / Q000191:economics* / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D013030:Spain; D014665:Vasodilator Agents / Q000191:economics / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D044062:Prostaglandins I; D014665:Vasodilator Agents; D011464:Epoprostenol; D016285:Iloprost; C427248:treprostinil