Cost Effectiveness of First-Line Oral Therapies for Pulmonary Arterial Hypertension: A Modelling Study

Abstract

Background In recent years, a significant number of costly oral therapies have become available for the treatment of pulmonary arterial hypertension (PAH). Funding decisions for these therapies requires weighing up their effectiveness and costs. Objective The aim of this study was to assess the cost effectiveness of monotherapy with oral PAH-specific therapies versus supportive care as initial therapy for patients with functional class (FC) II and III PAH in Canada. Methods A cost-utility analysis, from the perspective of a healthcare system and based on a Markov model, was designed to estimate the costs and quality-adjusted lifeyears (QALYs) associated with bosentan, ambrisentan, riociguat, tadalafil, sildenafil and supportive care for PAH in treatment-naïve patients. Separate analyses were conducted for cohorts of patients commencing therapy at FC II and III PAH. Transition probabilities, based on the relative risk of improving and worsening in FC with treatment versus placebo, were derived from a recent network metaanalysis. Utility values and costs were obtained from published data and clinical expert opinion. Extensive sensitivity analyses were conducted. Results Analysis suggests that sildenafil is the most costeffective therapy for PAH in patients with FC II or III. Sildenafil was both the least costly and most effective therapy, thereby dominating all other treatments. Tadalafil was also less costly and more effective than supportive care in FC II and III; however, sildenafil was dominant over tadalafil. Even given the uncertainty within the clinical inputs, the probabilistic sensitivity analysis showed that apart from sildenafil and tadalafil, the other PAH therapies had negligible probability of being the most cost effective. Conclusion The results show that initiation of therapy with sildenafil is likely the most cost-effective strategy in PAH patients with either FC II or III disease. Key Points for Decision MakersThe results indicate that initiation of therapy with sildenafil in patients with functional class (FC) II and III PAH would result in probable cost savings compared with riociguat, bosentan, ambrisentan 5 mg, ambrisentan 10 mg and tadalafil.The study findings do not support differential funding of PAH therapies for patients with FC II versus FC III disease based on current evidence.

Tetramethylpyrazine: A promising drug for the treatment of pulmonary hypertension

“…While these agents can improve haemodynamics, quality of life, and functional capacity, the worldwide usage of these drugs is largely limited by their high price. In Canada, PAH medications cost between Can$881 (tadalafil) and Can$4,028 (amberisentan) per month (Coyle et al, 2016). In the United States, the cost for bosentan and epoprostenol can be as much as $25,000 and $35,000 per month, respectively (Wryobeck, Lippo, McLaughlin, Riba, & Rubenfire, 2007).…”

Pharmacoeconomic analysis of medicines used in the treatment of pulmonary hypertension in the Russian Federation

“…Specifically, it was found that bosentan more often than ambrisentan caused hepatotoxicity which resulted in drug withdrawal. Considering different frequency of adverse effects with each drug, Kathryn Coyle et al 2016 [19] calculated QALY 1 values for ambrisentan and bosentan using a Markov model. For a patient with functional class II and 1 QALY (Quality-adjusted life year) is a year of perfect health.…”

“…The first one was based on the assumption that the compared drugs are equally effective and, hence, implied the use of the cost-minimization method. The second scenario was based on the results of Kathryn Coyle et al 2016 [19] whose conclusions were indicative of significant differences in QALY between ambrisentan and bosentan owing to different safety profiles of the two drugs. According to the methodology of pharmacoeconomic analysis, in the second scenario we should use the cost-utility analysis.…”

Treatment Selection in Pulmonary Arterial Hypertension: Phosphodiesterase Type 5 Inhibitors versus Soluble Guanylate Cyclase Stimulator

“…Endothelial NO synthase expression, NO production and NO availability are substantially reduced in patients with PAH, 5,10 so the sGC stimulator may be effective in patients who have not sufficiently responded to a PDE5 inhibitor. [34][35][36] The recent open-label, uncontrolled, phase…”

“…Treatment Response to PDE5 Inhibitor (RESPITE) study suggested that switching from PDE5 inhibitors to riociguat improved a range of clinical and haemodynamic endpoints in patients with PAH who have had an inadequate response to PDE5 inhibition. 34 Patients with PAH-systemic sclerosis (SSc) tend to have a worse prognosis than patients with idiopathic PAH, and have poorer responses to treatment and worse outcomes than those whose PAH is associated with other connective tissue diseases (CTDs). However, the long-term extension of the Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT-2) demonstrated the same survival at 2 years (93 %) for those with PAH-CTD and those with idiopathic or familial PAH who were receiving treatment with riociguat, despite more than half of the PAH-CTD patients having PAH-SSc.…”