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Proton pump inhibitors in systemic sclerosis: should we exercise caution? Insights from a large-scale data analysis
Irakli Tskhakaia1, Diego Lema2, Nanuka Tsibadze2
1Department of Medicine, Jefferson Einstein Hospital, 5501 Old York Road, Philadelphia, PA, 19141, USA. itskhakaia@uabmc.edu.
Clinical Rheumatology
|September 11, 2025
Summary
Systemic sclerosis patients on proton pump inhibitors (PPIs) face higher risks of chronic kidney disease and osteoporosis. However, PPIs remain crucial for managing GERD and lung issues in SSc patients, necessitating targeted monitoring.
Area of Science:
- Immunology
- Nephrology
- Gastroenterology
- Pharmacology
Background:
- Systemic sclerosis (SSc) frequently co-occurs with gastroesophageal reflux disease (GERD), requiring proton pump inhibitor (PPI) use.
- Long-term PPI safety concerns include chronic kidney disease (CKD), osteoporosis, and Alzheimer's disease.
- This study investigates if PPI adverse effects are amplified in SSc patients.
Purpose of the Study:
- To assess the amplified risks of PPIs in SSc patients compared to GERD patients.
- To evaluate the association between PPI use and CKD, osteoporosis, and neurodegenerative diseases in SSc.
- To provide real-world evidence on PPI safety in a large SSc cohort.
Main Methods:
- Retrospective observational analysis using the TriNetX research network (>130 million patients).
- Study population: 6800 SSc patients on PPIs and 1,889,433 GERD patients on PPIs.
- Propensity score matching and assessment of risks for CKD, osteoporosis, and dementia.
Main Results:
- SSc patients on PPIs showed significantly higher risks of CKD (AR 2.8%) and osteoporosis (AR 9%) post-matching.
- Minimal differences in advanced CKD stages (4, 5) were observed between SSc and GERD cohorts.
- SSc patients on PPIs exhibited a lower risk of Alzheimer's disease (AR -0.7%).
Conclusions:
- PPI therapy is essential for SSc management, despite potential increased risks of CKD and osteoporosis.
- The benefits of PPIs in mitigating GERD and pulmonary complications outweigh the amplified risks in SSc.
- Targeted monitoring for CKD and osteoporosis is recommended for SSc patients on long-term PPI therapy.
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