Long-Term Mortality and Morbidity Impact on Patients with Pulmonary Arterial Hypertension (PAH) If Access to Sotatercept Is Delayed: A Simulation Model

Abstract

Introduction: Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with significant morbidity and mortality. The phase 3 STELLAR trial tested sotatercept plus background therapy (BGT) versus placebo plus BGT, where BGT included mono-, double-, or triple-PAH targeted therapy. Building on the trial's findings, a population health model was recently published assessing the long-term clinical impact of sotatercept. This analysis expands on this model and compares the clinical outcomes of immediate treatment initiation with sotatercept plus BGT against delayed treatment initiation with sotatercept plus BGT using a six-state Markov-type model and over a lifetime horizon.

Methods: State-transition probabilities were obtained from STELLAR, while mortality rates adjusted for risk strata and probabilities of lung/heart-lung transplants were derived from COMPERA PAH registry data and literature.

Results: In the base case, a 2-year delay in treatment with sotatercept plus BGT resulted in an average of 12.4 years life expectancy, whereas immediate initiation of sotatercept led to an average of 16.5 years, a difference of 4.1 years. Immediate treatment with sotatercept plus BGT was also associated with a gain in infused prostacyclin-free life-years and resulted in 210 PAH hospitalizations avoided and 5 lung/heart-lung transplant avoided per 1000 patients.

Conclusions: This research suggests that early addition of sotatercept to BGT has the potential to increase life expectancy among patients with PAH and to reduce PAH hospitalizations, prostacyclin-use, and lung/heart-lung transplants needs. Real-world data are needed to confirm these findings, guiding clinicians and healthcare decision-makers in optimizing PAH treatment strategies.

Trial registration: ClinicalTrials.gov identifier, NCT04576988 (STELLAR).

Keywords: Pulmonary arterial hypertension; Risk strata; STELLAR; Sotatercept; Treatment delay.

Fig. 1

Model structure

Fig. 2

Base case results, estimated patient distribution by health state for all three treatment strategies. The patient distribution prior to half-cycle correction is shown above. The majority (around 75–80%) of patients receiving sotatercept plus BGT experience disease improvement in the first 1–3 years and then remain in the low-risk state for the remainder of their lifetime. In contrast, patients receiving BGT alone are more likely to experience disease progression within the same time frame, with over 80% of the patients remaining in the non-low risk health state afterwards. IH intermediate high, IL intermediate low, trans transplant