What are the expected benefits of adding sotatercept to a pulmonary arterial hypertension (PAH) treatment regimen consisting of sildenafil, ambrisentan, and epoprostenol in a patient with World Health Organization (WHO) functional class III PAH?

From the Guidelines

Based on the STELLAR trial findings, I would advise PJ that she may expect improved exercise capacity within 6 months from adding sotatercept to her current PAH medication regimen. The STELLAR trial demonstrated that patients receiving sotatercept in addition to background PAH therapy experienced significant improvements in exercise capacity as measured by the 6-minute walk distance 1. While sotatercept may help reduce her symptoms of shortness of breath during physical activity, it's essential for PJ to understand that it will not completely eliminate these symptoms. Some key points to consider:

• Sotatercept works by targeting the underlying disease pathways in PAH through inhibition of activin signaling, which helps restore balance between proliferative and anti-proliferative factors in the pulmonary vasculature.
• The medication is administered as a subcutaneous injection every 3 weeks.
• Common side effects include headache, diarrhea, and changes in hemoglobin levels.
• Regular follow-up appointments will be necessary to monitor her response to therapy and adjust treatment as needed.
• PJ should continue all her current medications (sildenafil, ambrisentan, and epoprostenol) while adding sotatercept to her regimen. It's also important to note that other treatments, such as sitaxentan and sildenafil, have shown efficacy in improving exercise capacity and hemodynamics in PAH patients 1. However, the STELLAR trial provides the most recent and highest quality evidence for the use of sotatercept in PAH, making it the preferred choice for PJ's treatment regimen. In terms of specific benefits, PJ may expect:
• Improved exercise capacity within 6 months
• Potential reduction in symptoms of shortness of breath during physical activity
• Regular monitoring and adjustments to her treatment regimen as needed.

From the FDA Drug Label

12.2 Pharmacodynamics PVR: A statistically significantly greater decrease from baseline in PVR was observed in the WINREVAIR group compared to the placebo group in the Phase 3 STELLAR study. The median treatment difference in PVR between sotatercept-csrk and placebo was -235 dynes*sec/cm5 (95% CI: -288, -181; p<0.001). NT-proBNP: A statistically significantly greater decrease from baseline in NT-proBNP was observed in the WINREVAIR group compared to the placebo group in the Phase 3 STELLAR study The median treatment difference in NT-proBNP between the sotatercept-csrk and placebo was -442 pg/mL (95% CI: -574, -310; p<0.001).

The potential benefits of adding sotatercept to PJ's medication regimen for PAH based on the findings from the STELLAR trial include:

• Improved exercise capacity: The reduction in PVR and NT-proBNP suggests that sotatercept may improve exercise capacity in patients with PAH.
• No information is provided about reduced risk of death within 90 days, improved cognition and emotions within 90 days, or elimination of shortness of breath during physical activity within 6 months in the STELLAR trial 2.

From the Research

Potential Benefits of Sotatercept for PAH

The potential benefits of adding sotatercept to PJ's medication regimen for PAH can be summarized as follows:

• Improved exercise capacity, as assessed by 6-minute walk distance, within 24 weeks 3, 4, 5, 6
• Delayed time to first occurrence of death or clinical worsening event 3, 7
• Reduced risk of a composite of death from any cause, lung transplantation, or hospitalization for worsening pulmonary arterial hypertension 7
• Improvements in pulmonary vascular resistance, World Health Organization functional class, and right ventricle structure and function 3, 5

Expected Outcomes

Based on the findings from the STELLAR trial, PJ may expect the following outcomes from adding sotatercept to her medication regimen:

• Improved exercise capacity within 6 months
• Reduced risk of death or clinical worsening events

Not Expected Outcomes

The following outcomes are not expected based on the available evidence:

• Elimination of shortness of breath during physical activity within 6 months
• Improved cognition and emotions within 90 days
• Reduced risk of death within 90 days is not explicitly stated in the provided studies, however, study 7 shows that death from any cause occurred in 7 patients (8.1%) in the sotatercept group and in 13 patients (15.1%) in the placebo group.