B106-06 Doxycyline Decreases Epistaxis Burden in PAH Patients Treated With Sotatercept: A Single Center Experience

Abstract Rationale Sotatercept, a ligand trap for members of the transforming growth factor-β superfamily, modulates proliferative signaling pathways implicated in both pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT). Consequently, HHT-like manifestations, particularly epistaxis, occur in 22-45% of treated patients. Doxycycline, a tetracycline with anti-angiogenic properties, has demonstrated modest efficacy in reducing epistaxis frequency in HHT. Given the shared pathogenic mechanisms, we hypothesized that doxycycline could mitigate epistaxis in PAH patients receiving sotatercept. Methods At a single academic center, we identified 19 of 240 PAH patients who developed de novo or worsening epistaxis following sotatercept initiation who did not respond to supportive measures such as nasal humidification. Patients using tranexamic acid or sclerotherapy, or those with active infection or doxycycline allergy, were excluded. Fifteen patients started doxycycline 100 mg orally twice daily for six weeks. Epistaxis severity was assessed using the Epistaxis Severity Score (ESS) at baseline and follow-up. Results Baseline characteristics are summarized in Table 1. Most patients were female (79%), with a mean age of 53.6 years. Epistaxis developed de novo in 19 patients and worsened in 2 within three months of sotatercept initiation. Four patients were on anticoagulation (1 warfarin, 3 apixaban) that was continued. Four patients declined therapy and opted for supportive care. At six-week follow-up, 10 of 15 patients (67%) reported marked improvement (mean ESS decreased by 50%, from 2.24 to 0.85), including complete resolution of bleeding in 4 patients (25%) without recurrence. Most patients reported improvement in epistaxis within 2-4 days of treatment. One patient with gingival bleeding reported improvement in symptoms while on doxycycline as well. Of the five patients who did not experience improvement in bleeding, two were on anticoagulation. Doxycycline was well tolerated, and no adverse effects were reported. Among the four patients who did not receive doxycycline, one discontinued sotatercept due to persistent bleeding. All other patients were maintained on current sotatercept doses without adjustment. Conclusion Doxycycline may reduce epistaxis severity and frequency in PAH patients experiencing sotatercept-associated bleeding due to its anti-angiogenic effects. This well-tolerated intervention warrants further prospective evaluation as a potential adjunctive therapy for managing mild epistaxis in this population. This abstract is funded by: none