Despite advances in pharmacological options, PAH remains a severe and complex disease. Current standard treatment for advanced PAH often includes triple therapy, which incorporates agents targeting the prostacyclin pathway. These medications, frequently administered parenterally rather than orally, are effective but come with significant side effects, logistical challenges, and a considerable impact on patients’ daily lives.

As part of the current Publication of the Month, BREATH presents a new article in the European Respiratory Journal that addresses a clinically highly relevant question. Under the title “Withdrawal of prostacyclin pathway therapies after initiation of sotatercept treatment in patients with pulmonary arterial hypertension,” BREATH researchers Prof. Dr. Karen M. Olsson and Dr. Jan Fuge (shared first authorship), together with Dr. Da-Hee Park, Dr. Jan C. Kamp, and Prof. Dr. Marius M. Hoeper, report on their experience with the stepwise withdrawal of prostacyclin therapies following initiation of treatment with the newly approved drug sotatercept.

This retrospective analysis includes female patients from Hannover Medical School (MHH) who were treated with sotatercept as part of clinical trials and had previously received triple therapy. Remarkably, all seven patients treated with the oral prostacyclin alternative selexipag were able to fully discontinue the medication within a few months—without any signs of clinical deterioration. Even in the more complex cases involving intravenous or subcutaneous treprostinil, discontinuation was successfully achieved in about one third of the cases. Patients who experienced clinical worsening during the course of treatment were stabilized through resumption or dose escalation of prostacyclin therapy.

“Our results show that, for the first time, sotatercept allows us to re-evaluate established PAH treatment concepts on an individual basis,” explains Prof. Dr. Karen M. Olsson. “In the future, we may be able to deliberately reduce treatment burden—tailored to the clinical stability and life circumstances of our patients.”

These observations suggest that sotatercept not only complements existing therapies but may also, under certain conditions, allow for therapy reduction with potential gains in quality of life. This opens up new therapeutic possibilities, particularly for patients who suffer from the side effects or daily limitations associated with prostacyclin treatment. Decisions regarding discontinuation were made on a case-by-case basis, guided by functional and hemodynamic parameters, and in close consultation with the patients.

Clinical implication: For stable patients receiving sotatercept, a stepwise reduction of therapy may be considered—provided it is closely monitored and based on clearly defined criteria for potential re-initiation. The long-term consequences of this approach remain to be fully understood and require further prospective studies.

You can access the original publication here.

Text: BREATH/ AB

Photo: MHH/Figiel