- Design
- Registry cohort with propensity-score weighting
- Population
- 10,660 patients with systemic sclerosis in EUSTAR
- Primary outcome
- All-cause mortality and ILD progression
- Effect
- Mortality HR 1.88 (95% CI 1.40–2.54), minimal absolute difference; no effect on meaningful FVC decline
Using the EUSTAR registry, this study followed 10,660 people with systemic sclerosis for a mean of almost six years; 81% took a proton pump inhibitor at some point. PPI users had more severe gastrointestinal, lung and vascular disease. Statistical weighting was used to account for the reasons PPIs were prescribed.
PPI exposure was associated with higher all-cause mortality (HR 1.88), but the absolute difference in survival at five years was minimal, and the authors suggest this might reflect sicker patients, though without cause-of-death data a drug effect cannot be excluded. PPIs were not associated with less clinically meaningful lung volume decline, and the modest slowing of gas-transfer decline made little absolute difference.
The finding does not argue against PPIs for reflux, which is common and troublesome in systemic sclerosis. It does argue against expecting them to protect the lungs. It was published in September 2026.
- Continue PPIs for symptomatic reflux in systemic sclerosis.
- Do not rely on PPIs to slow interstitial lung disease.
- The mortality association may reflect disease severity, but without cause-of-death data a drug effect cannot be excluded.
- Review long-term PPI need periodically, as for any patient.
Why it matters
It corrects a hope that acid suppression might protect the lungs in systemic sclerosis.
Don't overread it
The authors suggest the mortality association may reflect disease severity; a drug effect cannot be excluded.
The statistics, in plain English
A hazard ratio of 1.88 sounds large, but the restricted mean survival time, which measures absolute survival over five years, differed only minimally. When sicker patients are more likely to receive a drug, even careful weighting may not remove that bias.
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