Systemic sclerosis PAH: sustained early therapy linked to survival, with a caveat

Design

Registry cohort analysis, as-treated and intention-to-treat

Population

301 treatment-naive patients with systemic sclerosis-associated PAH, EUSTAR 2000 to 2021

Primary outcome

All-cause mortality and 36-month PAH progression

Effect

As-treated combination therapy HR 0.40 (95% CI 0.18 to 0.88); no association on intention-to-treat

A EUSTAR registry analysis examined 301 treatment-naive patients with systemic sclerosis-associated pulmonary arterial hypertension diagnosed between 2000 and 2021 who met the 2022 haemodynamic definition. Published in Arthritis & Rheumatology on 15 October 2026.

Two thirds started PAH therapy within four months of right heart catheterisation. Treatment was started in 31% of those with milder haemodynamics (mPAP 21 to 24 mmHg or PVR 2 to 3 WU) against 79% meeting the older definition. Combination therapy rose from 14% in low-risk to 67% in high-risk patients. Over a median 3.9 years, 42% died. In as-treated analyses, sustained monotherapy (HR 0.50, 95% CI 0.27 to 0.92) and combination therapy (HR 0.40, 0.18 to 0.88) were associated with lower mortality, but intention-to-treat analyses showed no association.

The contrast between the two analyses is the main lesson: patients who stay on treatment differ from those who stop, so the survival gain may partly reflect who tolerated therapy. The results support prompt, risk-stratified treatment and highlight how often patients with milder haemodynamics go untreated.

• Screen patients with systemic sclerosis for pulmonary hypertension at least annually
• Use current risk stratification to choose monotherapy or combination therapy
• Discuss treatment for patients with milder haemodynamics, who were often left untreated
• Work with a pulmonary hypertension centre on initial treatment

Why it matters

Mortality in this group remains very high, and treatment practice still varies.

Don't overread it

Observational; the benefit disappeared in intention-to-treat analysis, suggesting selection effects.

The statistics, in plain English

As-treated analysis compares patients by what they actually took; intention-to-treat compares them by what was started. When only the first shows benefit, those who stayed on treatment may simply have been healthier.

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