Risk of systemic autoimmune diseases in gastric disease patients with proton pump inhibitor use: a nationwide cohort study in Taiwan

Introduction The risk factors for systemic autoimmune diseases (SAD) in gastric disease patients with proton pump inhibitor (PPI) use are still unclear. This study discussed this relationship in an Asian population. Methods Patients without a prior history of SAD were identified from Taiwan’s National Health Insurance Research Database between January 1, 2000, and December 31, 2010. Cox regression models were applied to estimate the hazard ratio (HR) with 95% confidence interval [CI] of SAD. The cumulative PPI dosage was stratified by quartiles of defined daily doses and adjusted for baseline disease risk score which served as the primary variables compared against no PPI use. Results We analyzed the data of 51,291 participants aged 18 years or older and free of SAD at baseline. PPI users ( n = 17,938) had a significantly increased risk of SAD over non-PPI users. There was a significantly higher risk of developing SAD in older age groups. A significant dose-dependent association was observed between cumulative PPI use and the risk of SAD. Female PPI users had significantly higher risk of developing SAD. In patients who received PPI, the autoimmune disease with significantly higher incidence was Sjögren syndrome (SjS) (adjusted HR [aHR] 1.82, 95% CI, 1.02–3.27) and rheumatoid arthritis (RA) (aHR, 2.19, 95% CI, 1.19–4.01). Conclusion This study found PPI users to be associated with an increased risk of SAD. Older age or cumulative PPI use was significantly associated with SAD, and the highest incidence was SjS and RA among gastric disease patients who received PPI. Key Points • This nationwide long-term cohort study found PPI users to be associated with an increased risk of rheumatoid arthritis and Sjögren syndrome in Taiwan. • This finding may help with clinical risk evaluation and will inform further investigation of the pathogenesis between autoimmune diseases and PPI use.