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.

Background Pharmacovigilance reports have suggested that certain commonly used medications may trigger autoimmune diseases (ADs) and immune-mediated inflammatory diseases (IMIDs). We systematically reviewed the literature to evaluate whether psychiatric medication use is associated with ADs and IMIDs. Methods The protocol was registered in PROSPERO (CRD42022296524) before the start of the study. We searched Medline Ovid and Scopus up to November 28th, 2021, for comparative studies, with any psychiatric medication as exposure and ADs and IMIDs as outcomes. Meta-analysis was performed using DerSimonian-Laird random-effects modeling. The PRISMA 2020 guidelines were followed in reporting. Study-level risk of bias was assessed using the Newcastle-Ottawa Scale, and the overall certainty of evidence using GRADE. Results There were 7,265 citations from which 31 studies were eligible, all from high-income countries, covering 15 distinct immune diseases. The evidence for the association between selective serotonin reuptake inhibitor (SSRI) use and higher risk of microscopic colitis (meta-OR 2.60, 95% CI 1.05–6.39, I2 97.5%, 6 studies) was of low certainty. A subgroup analysis by the histological type of microscopic colitis showed a statistically significant association only with lymphocytic colitis (meta-OR 2.88, 95% CI 2.60–3.18, I2 00.00%, three studies). In two case-control studies, SSRI use had no significant association with psoriasis (meta-OR 0.80, 95% CI 0.58–1.10, I2 82.4%). The risk of acute pancreatitis was slightly increased with exposure to SSRIs (meta-OR 1.13, 95% CI 1.01–1.26, I2 00.0%), as was the risk of bullous pemphigoid after exposure to antipsychotics (meta-OR 1.79, 95% CI 1.17–2.73, I2 0%). Conclusions We reviewed the literature on whether psychiatric medications associate with the risk of ADs and IMIDs and concluded that, despite several signals, the credibility of evidence remains low at best. Prospective cohort studies would be needed as the next step to confirm the suggestions of increased risk.