Post-marketing vascular ectasia and regional bleeding reports with sotatercept in pulmonary arterial hypertension: a disease-restricted active-comparator pharmacovigilance study

Abstract

Abstract Background Sotatercept has introduced a disease-modifying treatment strategy for pulmonary arterial hypertension (PAH), but early post-marketing reports require interpretation beyond labelled bleeding and haematological events. We aimed to characterise structural vascular/ectasia-related reporting patterns and regional bleeding in a PAH-restricted active-comparator pharmacovigilance study. Results FDA Adverse Event Reporting System/Adverse Event Monitoring System reports from 2024 Q2 through 2026 Q1 were deduplicated and restricted to definite-PAH reports. The primary cohort included 2,121 sotatercept primary-suspect reports and 19,557 active-comparator primary-suspect reports for other PAH-targeted therapies. Sotatercept showed disproportionate structural vascular/ectasia reporting (38/2,121 [1.8%] vs 9/19,557 [0.05%]; reporting odds ratio [ROR] 39.62, 95% CI 19.13–82.06). The signal was not limited to telangiectasia-related terms: non-telangiectasia vascular structural terms remained disproportionate (14/2,121 [0.66%] vs 8/19,557 [0.04%]; ROR 16.24, 95% CI 6.80–38.75), and the composite without co-reported telangiectasia remained disproportionate. Non-laboratory haemorrhage was also disproportionate (555/2,121 [26.2%] vs 1,763/19,557 [9.0%]; ROR 3.58, 95% CI 3.21–3.99), persisting after exclusion of epistaxis and selected local or traumatic terms. Among sotatercept bleeding reports with serious outcome codes, gastrointestinal bleeding accounted for the largest share. Platelet-related and erythroid-related composites showed strong disproportionality and were interpreted as monitoring-context findings. Coded hereditary haemorrhagic telangiectasia/arteriovenous malformation background indications were not recorded in sotatercept reports, and excluding reports with these indications did not materially alter the core estimates. Penalised, reporter/region and source-quarter sensitivity models supported the stability of the structural vascular signal. Conclusions In PAH reports, sotatercept was associated with disproportionate reporting of structural vascular/ectasia-related terms, alongside regional bleeding and haematological findings. These reporting associations do not establish causality or confirm a biological mechanism and warrant further evaluation in longitudinal PAH studies. Clinical trial number Not applicable.

The authors' abstract, as published at the source. Orphanet Journal of Rare Diseases, 2026 · DOI ↗