What is the role of Sotatercept (Luspatercept) in the treatment of pulmonary veno-occlusive disease?

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Last updated: March 21, 2025View editorial policy

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From the Guidelines

Sotatercept is not currently recommended for pulmonary veno-occlusive disease (PVOD). While sotatercept has shown promise in treating pulmonary arterial hypertension (PAH) by targeting the activin signaling pathway, its use in PVOD specifically has not been established through clinical trials 1. PVOD is a rare form of pulmonary hypertension characterized by progressive occlusion of pulmonary veins and venules, and it typically responds poorly to standard PAH therapies. In fact, vasodilator therapies used for PAH can be dangerous in PVOD patients, potentially causing pulmonary edema.

Current Management of PVOD

The current management of PVOD focuses on:

  • Supportive care
  • Oxygen therapy
  • Diuretics for fluid management
  • Early referral for lung transplantation, which remains the only definitive treatment 1. Given the distinct pathophysiology of PVOD compared to PAH, any novel therapies like sotatercept would require specific evaluation in this patient population before being recommended.

Importance of Specialized Care

Patients with suspected PVOD should be managed at specialized centers with expertise in pulmonary hypertension and transplantation, as they are at high risk of lung edema after the initiation of PAH-specific drug therapy 1. Referral of patients with PVOD to a transplant centre for evaluation is indicated as soon as the diagnosis is established, highlighting the importance of early and specialized care in managing this condition.

From the Research

Role of Sotatercept in Pulmonary Veno-Occlusive Disease

There is limited information available on the role of Sotatercept (Luspatercept) in the treatment of pulmonary veno-occlusive disease (PVOD). The provided studies primarily focus on the treatment of pulmonary arterial hypertension (PAH) with Sotatercept.

Sotatercept Mechanism and PAH Treatment

  • Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA), leading to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2 2, 3, 4, 5.
  • This mechanism activates an antiproliferative signalling to the cells of the pulmonary arteries and arterioles, aiming to rebalance the proliferative and antiproliferative pathway that characterizes PAH 2, 3, 4, 5.
  • Sotatercept has been shown to improve exercise capacity, reduce the risk of clinical worsening events, and improve WHO functional class in patients with PAH 2, 3, 4, 5.

Pulmonary Veno-Occlusive Disease Treatment

  • The provided studies do not specifically address the use of Sotatercept in the treatment of PVOD 6, 2, 3, 4, 5.
  • One study mentions that lung transplantation is the only successful therapeutic option for patients suffering from PVOD, but does not discuss Sotatercept as a treatment option 6.

Conclusion Not Provided

As per the instructions, no conclusion will be drawn from the available evidence. The information provided highlights the role of Sotatercept in PAH treatment but does not offer insights into its use for PVOD.

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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