Antibiotic use and the risk of rheumatoid arthritis: A population-based case-control study

Background: Antibiotic-induced disturbances of the human microbiota have been implicated in the development of chronic autoimmune conditions. This study aimed to assess whether antibiotic use is associated with the onset of rheumatoid arthritis (RA). Methods: A nested case-control study was conducted utilising data from the primary care Clinical Practice Research Datalink (CPRD). Patients with an incident diagnosis of RA were identified (1995-2017). Each case was matched on age, gender, and general practice to ≥ 5 controls without RA. Conditional logistic regression was used to examine previous antibiotic prescriptions and RA onset after controlling for confounding factors. Results: We identified 22,677 cases of RA, matched to 90,013 controls, with a median follow-up of 10 years before RA diagnosis. The odds of developing RA were 60% higher in those exposed to antibiotics than in those not exposed (OR 1.60; 95% CI 1.51-1.68). A dose- or frequency-dependent association was observed between the number of previous antibiotic prescriptions and RA. All classes of antibiotics were associated with higher odds of RA, with bactericidal antibiotics carrying higher risk than bacteriostatic (45% vs. 31%). Those with antibiotic-treated upper respiratory tract (URT) infections were more likely to be RA cases. However, this was not observed for URT infections not treated with antibiotics. Antifungal (OR = 1.27; 95% CI 1.20-1.35) and antiviral (OR = 1.19; 95% CI 1.14-1.24) prescriptions were also associated with increased odds of RA. Conclusion: Antibiotic prescriptions are associated with a higher risk of RA. This may be due to microbiota disturbances or underlying infections driving risk. Further research is needed to explore these mechanisms.