Which patient with Pulmonary Arterial Hypertension (PAH) is a suitable candidate for sotatercept treatment based on the STELLAR trial findings?

From the Guidelines

The most appropriate patient case scenario to include in your educational program would be the 43-year-old female with WHO Group 1, functional class III PAH who has persistent symptoms despite treatment with sildenafil, ambrisentan, and treprostinil. This patient meets the criteria as she has WHO Group 1 PAH, is functional class III, and remains symptomatic despite being on multiple PAH therapies, which is in line with the recommendations for PAH treatment outlined in the Chest guideline and expert panel report 1. The STELLAR trial specifically enrolled patients with WHO Group 1 PAH who were symptomatic (functional class II-III) despite receiving stable doses of background PAH therapy, making this patient an ideal example for illustrating the use of sotatercept in PAH treatment. Additionally, her laboratory values are appropriate for sotatercept treatment, with normal liver function tests and a hemoglobin level that is not elevated (13.6 g/dL), which is consistent with the guidelines for PAH treatment 1. The other cases would be inappropriate because they either involve a patient with WHO Group 2 PAH (heart failure-related, which was excluded from STELLAR), a patient with controlled symptoms (not meeting the requirement for symptomatic disease), or a patient with significantly elevated hemoglobin (17.3 g/dL), which would be a concern given that sotatercept can increase hemoglobin levels and potentially lead to thrombotic complications, as noted in the European Society of Cardiology guidelines for PAH diagnosis and treatment 1. Some key points to consider when selecting a patient case scenario include:

• The patient should have WHO Group 1 PAH, as this is the population that was enrolled in the STELLAR trial
• The patient should be symptomatic (functional class II-III) despite receiving stable doses of background PAH therapy
• The patient's laboratory values should be appropriate for sotatercept treatment, with normal liver function tests and a hemoglobin level that is not elevated.

From the FDA Drug Label

The efficacy of WINREVAIR was evaluated in adult patients with PAH in the STELLAR trial (NCT04576988). STELLAR was a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which 323 patients with PAH (WHO Group 1 FC II or III) were randomized 1:1 to WINREVAIR (target dose 0. 7 mg/kg) (n=163) or placebo (n=160) administered subcutaneously once every 3 weeks. The most appropriate patient case scenario to include as an example based on the findings from the STELLAR trial is:

• A 43-year-old female with World Health Organization (WHO) Group 1, functional class III PAH; persistent symptoms despite treatment with sildenafil, ambrisentan, and treprostinil; and blood pressure 130/56 mm Hg, platelet count 210 x 103 cells/mm3, hemoglobin (Hgb) 13.6 g/dL, and liver function tests (LFTs) within normal limits. This patient meets the criteria of the STELLAR trial, which included patients with WHO Group 1 PAH and functional class II or III symptoms 2.

From the Research

Patient Case Scenarios for Sotatercept Treatment

To determine the appropriate patient case scenario for illustrating the use of sotatercept in treating pulmonary arterial hypertension (PAH), we must consider the findings from relevant studies, including the STELLAR trial 3. The STELLAR trial investigated the efficacy of sotatercept in patients with PAH at high risk for death, indicating its potential benefits in advanced cases.

Eligibility Criteria

The STELLAR trial focused on patients with World Health Organization (WHO) functional class III or IV PAH and a high 1-year risk of death, as determined by the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management Lite 2 risk score (≥9) 3. Patients were receiving the maximum tolerated dose of background therapy.

Case Scenario Analysis

Given the criteria and focus of the STELLAR trial, let's analyze the provided patient case scenarios:

• A 43-year-old female with WHO Group 1, functional class III PAH; persistent symptoms despite treatment with sildenafil, ambrisentan, and treprostinil: This patient's profile aligns with the advanced PAH condition and the need for additional therapy due to persistent symptoms despite being on multiple background treatments.
• A 62-year-old male with WHO Group 1, functional class II PAH; controlled symptoms on tadalafil and ambrisentan: This patient is in functional class II and has controlled symptoms, which does not align with the high-risk profile targeted in the STELLAR trial.
• A 46-year-old female with newly diagnosed WHO Group 1, functional class III PAH; planned to start tadalafil: This patient is newly diagnosed and about to start treatment, not fitting the profile of being on maximum tolerated background therapy.
• A 55-year-old male with WHO Group 2, functional class III PAH; on maximized heart failure treatments: This patient has WHO Group 2 PAH, which is not the focus of the STELLAR trial or typical sotatercept treatment scenarios described.

Appropriate Case Scenario

Based on the information provided and the focus of the STELLAR trial, the most appropriate patient case scenario to include as an example for the use of sotatercept in treating PAH would be:

• The 43-year-old female with WHO Group 1, functional class III PAH, who has persistent symptoms despite being on sildenafil, ambrisentan, and treprostinil, as her condition and treatment history align with the criteria for sotatercept therapy as investigated in the STELLAR trial 3.

Key points to consider in selecting a case scenario include:

• The patient's WHO functional class and PAH group
• The presence of persistent symptoms despite background therapy
• The patient's risk profile for death or clinical worsening, as would be assessed by tools like the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management Lite 2 risk score.