Influence of prior antibiotic use on risk of rheumatoid arthritis: Case control study in general practice

Objectives: To test the hypothesis that prior antibiotics influences the risk of developing RA. Methods: A case-control study was conducted over 15 years using the UK's Royal College of General Practitioners Research and Surveillance Centre database. The frequency and type of antibiotic prescription for patients who subsequently developed RA were compared with antibiotic prescriptions in a control group of patients who remained free of RA. Cases, defined as patients with a new diagnosis of RA made between 2006 and 2018, were matched with up to four RA-free controls on practice, age, gender and date of diagnosis. Exposure was measured by the number and type of prescriptions for antibiotics prior to the RA diagnosis or to the index date in controls. Results: A total of 8482 patients with a new diagnosis of RA between 2006 and 2018 were compared with 22 661 controls. There was a higher likelihood of an RA diagnosis after antibiotic prescriptions within 1 year, 5 years and ever with a strong dose-response. Patients receiving >10 antibiotics in a 5 year period were more than twice as likely to receive an RA diagnosis as controls [adjusted odds ratio 2.65 (CI 2.40, 2.93)]. Conclusion: Exposure to antibiotics prior to the diagnosis was a significant risk factor for RA. This could reflect an immunological response to a compromised microbiome. Alternatively, patients with pre-symptomatic or early undiagnosed RA may have been more likely to present to their general practitioner with infections due to an unrecognized effect of RA.