Affiliations: [a] Independent Researcher, Groningen, The Netherlands | [b] Hatanpää Health Centre, City of Tampere, Tampere, Finland | [c] Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland
Correspondence:
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Address for correspondence: Anna Nevalainen, Independent Researcher, Tampere, Finland. E-mail: [email protected]
Abstract: BACKGROUND:Pharmacovigilance risk signals have proposed a relationship between the use of acid-suppressive medications and the development of certain autoimmune and immune-mediated inflammatory diseases. OBJECTIVE:A systematic review and a meta-analysis was performed. METHODS:We reviewed MEDLINE (Ovid) and Scopus for comparative observational studies between these diseases and previous exposure to proton-pump inhibitors (PPI), H2-receptor antagonists (H2RA), and antacids. The protocol was registered on the PROSPERO database (CRD42020192715). RESULTS:From 3,191 citations, 25 articles were eligible and covered 16 diseases. Microscopic colitis (MC) was studied the most (7 studies). In a random-effects meta-analysis, there was low certainty evidence (GRADE approach) of a non-significant relationship between exposure to any PPIs and MC (meta-OR 3.28, 95% CI 0.98–11.0, I2 98.2%, six studies, 4,436 PPI-exposed MC patients). Moderate certainty evidence pointed towards large odds of collagenous colitis after exposure to lansoprazole (meta-OR 14.5, 95% CI 9.37–22.3, I2 10.2%, three studies, 1,725 lansoprazole-exposed patients). After PPI exposure, the risk of rheumatoid arthritis was slightly increased based on low certainty evidence from two cohort studies totaling 475 diagnoses (meta-RR 1.62, 95% CI 1.12–2.34, I2 34.5%). CONCLUSIONS:In patients with MC, it would be reasonable to carefully review the indication of PPI, especially in CC patients using lansoprazole.
