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. 2025 Aug;42(8):3902-3921.
doi: 10.1007/s12325-025-03241-4. Epub 2025 Jun 17.

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

Adnan Alsumali  1 , Vallerie McLaughlin  2 , Jestinah Chevure  3 , Rogier Klok  4 , Wenjie Zhang  5 , Eliana C Martinez  4 , Christine Pausch  6 , Janethe De Oliveira Pena  4 , Gijs van de Wetering  7 , Murvin Jootun  3 , Dominik Lautsch  4 , Marius M Hoeper  8
Affiliations

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

Adnan Alsumali et al. Adv Ther. 2025 Aug.

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.

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Conflict of interest statement

Declarations. Conflict of Interest: Wenjie Zhang and Gijs van de Wetering are employees of OPEN Health, which received funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, to conduct the study. Adnan Alsumali, Janethe de Oliveira Pena, Rogier Klok, Dominik Lautsch, Jestinah Chevure, Murvin Jootun and Eliana Martinez are employees or were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, at the time the study was done and may hold stock in Merck & Co., Inc., Rahway, NJ, USA. Vallerie McLaughlin is a consultant for Aerovate, Altavant Sciences, Bayer, CVS Caremark, CorVista Health, Gossamer Bio, Janssen, Merck, and United Therapeutics; has received grants from Aerovate, Altavant Sciences, Merck, Gossamer Bio, Janssen, and SoniVie; and received stock from Clene. Christine Pausch has nothing to disclose. Marius M. Hoeper is a consultant and speaker for Acceleron Pharma, Inc., Actelion, AOP Orphan Pharmaceuticals, Bayer, Ferrer, GlaxoSmithKline, Janssen, and MSD. Ethical Approval: This study relied on previously conducted studies and did not involve any new studies requiring the direct participation of human subjects; thus, ethics board approval was not required. The authors sought and received permission from the registry owners to access and use data from the COMPERA PAH registry.

Figures

Fig. 1
Fig. 1
Model structure
Fig. 2
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
See this image and copyright information in PMC

References

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