Systemic sclerosis-associated pulmonary hypertension: why disease-specific composite endpoints are needed

Area of Science:

• Cardiology and Rheumatology
• Clinical Trial Design and Endpoints

Background:

• Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc).
• PAH associated with SSc (PAH-SSc) is often clinically grouped with idiopathic PAH (IPAH) in research.
• Current pivotal studies primarily use exercise capacity as the main endpoint.

Purpose of the Study:

• To discuss and evaluate potential clinical endpoints for PAH-SSc.
• To highlight the limitations of using IPAH endpoints for PAH-SSc.
• To advocate for tailored endpoint strategies in PAH-SSc clinical trials.

Main Methods:

• Review and discussion of existing and proposed clinical endpoints for PAH.
• Comparative analysis of clinical outcomes and management strategies between IPAH and PAH-SSc.
• Literature review focusing on the appropriateness of endpoints in different PAH subtypes.

Main Results:

• Composite clinical endpoints may offer a more meaningful reflection of long-term outcomes than exercise capacity alone.
• Significant differences exist in clinical outcomes and management between IPAH and PAH-SSc.
• Current endpoints, primarily focused on exercise capacity, may not be suitable for both IPAH and PAH-SSc.

Conclusions:

• Standardized endpoints for IPAH may not adequately capture the nuances of PAH-SSc.
• Tailoring endpoints to the specific characteristics of PAH-SSc is crucial for therapeutic progress.
• Failure to adapt endpoints could hinder advancements in managing PAH in systemic sclerosis patients.