Real-World Sotatercept Eligibility: Analysis from the FOCUS-PAH Registry.

Abstract

Introduction: Pulmonary arterial hypertension (PAH) remains burdened by suboptimal outcomes despite contemporary therapy. Sotatercept showed clinical benefit in STELLAR and ZENITH, yet trial criteria may limit real-world implementation. We quantified real-world eligibility at baseline and during follow-up and identified baseline predictors of non-eligibility.

Methods: We retrospectively analyzed 657 patients with incident PAH (2001-2024), excluding 116 with incomplete follow-up data. Inclusion criteria mirroring STELLAR were WHO functional class II/III, PVR ≥5 WU, and stable background therapy. Exclusion criteria included severe comorbidities or recent cardiovascular events. Multivariable models identified predictors of non-eligibility. Extended eligibility per ZENITH criteria was also assessed.

Results: Among 541 analyzed patients, 104 (19%) were ineligible at baseline, mainly due to non-permitted PAH subtypes (71%) or vasoreactivity (29%). During a median 45-month follow-up, cumulative follow-up eligibility (i.e., patients who met criteria at least once after baseline) was 50%, with most exclusions due to PVR <5 WU (53%) or recent therapy changes (53%). Older age (HR 1.011, p = 0.003) and triple therapy (HR 2.841, p < 0.001) predicted non-eligibility, while idiopathic PAH was protective (HR 0.742, p = 0.025). Integrating ZENITH criteria increased eligibility to 56% (+6% vs. STELLAR).

Conclusion: STELLAR criteria exclude a substantial portion of real-world PAH patients, particularly during follow-up, when therapy intensification is often required per the 7th World Symposium algorithm. ZENITH criteria offer only a modest improvement. Tailored selection strategies and optimal timing for initiation are needed to enhance sotatercept's applicability. Future trials should consider enrichment strategies to broaden treatment eligibility.