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

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Abstract

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.

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Funding

This study is supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW108-TDU-B-212-133004); China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021); MOST Clinical Trial Consortium for Stroke (MOST 108-2321-B-039-003-); Tseng-Lien Lin Foundation, Taichung, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan.

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Authors and Affiliations

  1. Institute of Pharmacy, China Medical University, Taichung, Taiwan

    Hung-Yi Chen

  2. Department of Pharmacy, China Medical University Hospital, Beikang Campus, Yunlin, Taiwan

    Hung-Yi Chen

  3. Department of Pharmacy, Feng-Yuan Hospital, Ministry of Health Welfare, No. 100 An-Kan Rd., Fengyuan Dist., Taichung City, 42055, Taiwan, Republic of China

    Jiun-Jie Lin

  4. Taichung City New Pharmacist Association, Taichung, Taiwan

    Jiun-Jie Lin

  5. Institute of Lipids Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China

    Bo Yang

  6. Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan

    Mei-Chen Lin

  7. College of Medicine, China Medical University, Taichung, Taiwan

    Mei-Chen Lin

Authors
  1. Hung-Yi Chen
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  2. Jiun-Jie Lin
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  3. Bo Yang
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Contributions

Jiun-Jie Lin: revising the protocol for content and clarity; conception of the initial review; drafting the protocol; literature search; selecting, reading, and comparing titles, abstracts, and papers; drafting a data extraction sheet; data extraction; drafting the first review; reading and correcting the full review; and final approval.

Hung-Yi Chen and Bo Yang: building a database for data extraction, drafting a data extraction sheet, drafting the update review, and final approval.

Mei-Chen Lin and Management Office for health data Workgroup: data extraction and statistical analyses.

Corresponding author

Correspondence to Jiun-Jie Lin.

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Ethics approval

This study was approved by the China Medical University and China Medical University Hospital, Taiwan (CMUH104-REC2-115(CR-2)).

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Chen, HY., Lin, JJ., Yang, B. et al. Risk of systemic autoimmune diseases in gastric disease patients with proton pump inhibitor use: a nationwide cohort study in Taiwan. Clin Rheumatol 39, 2773–2780 (2020). https://doi.org/10.1007/s10067-020-05012-8

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  • DOI: https://doi.org/10.1007/s10067-020-05012-8

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