What is the role of sotatercept (a selective ligand trap for members of the transforming growth factor-beta superfamily) in the management of Pulmonary Arterial Hypertension (PAH)?

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From the Research

Sotatercept is a viable add-on therapy for patients with PAH Group 1 and functional class II-III, as it has been shown to improve exercise capacity, pulmonary vascular resistance, and NT-proBNP levels, with a recommended dosage of 0.3 mg/kg administered subcutaneously every 3 weeks, with potential dose increases to 0.7 mg/kg based on patient response and tolerability 1. The use of sotatercept in the management of Pulmonary Arterial Hypertension (PAH) is supported by recent clinical trials, including the STELLAR trial, which demonstrated significant improvements in exercise capacity, pulmonary vascular resistance, and NT-proBNP levels 1, 2.

Key Points

  • Sotatercept works by restoring balance in the TGF-beta signaling pathway, which is dysregulated in PAH, by acting as a trap for activins and growth differentiation factors, thereby reducing vascular remodeling and improving pulmonary vascular function 3.
  • The FDA approved sotatercept (brand name Winrevair) in March 2024 for adults with PAH WHO Group 1 functional class II-III 2.
  • Common side effects include headache, diarrhea, fatigue, and increased hemoglobin levels, which require regular monitoring 4, 2.
  • Patients should have their hemoglobin checked before treatment initiation, monthly for the first 3 months, and periodically thereafter 2.

Long-Term Efficacy and Safety

The SOTERIA study, an ongoing open-label study, has provided interim results on the long-term safety, tolerability, and efficacy of sotatercept in participants with PAH, with improvements in 6MWD, NT-proBNP, WHO FC, and SFRS achieved from baseline of SOTERIA largely maintained at one year 5.

Clinical Use

Sotatercept represents a novel therapeutic approach for PAH by targeting the underlying pathobiology rather than just managing symptoms, potentially offering better outcomes for patients with this progressive and life-threatening condition 1, 2. It is essential to note that sotatercept is used as an add-on therapy to existing PAH treatments rather than as monotherapy, and its use should be guided by the most recent clinical evidence and guidelines 1, 2.

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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