Rheumatoid Arthritis Risk Linked With Previous Antibiotic Exposure

Researchers assessed the risk for rheumatoid arthritis in patients receiving antibiotics.

Frequent use of prescribed antibiotics is associated with an increased risk for rheumatoid arthritis (RA), according to research results published in BMC Medicine.

Using data from a large, United Kingdom-based primary care cohort, researchers investigated the link between antibiotic prescriptions and RA onset. The nested case-control study extracted patient information from the primary care Clinical Practice Research Datalink. Patients with an incident RA diagnosis between 1995 and 2017 were included and matched with ≥5 healthy controls, based on age, sex, and general practice.

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A total of 22,677 patients in RA group were individually matched with 90,013 in the control group. A larger percentage of patients in the RA group vs those in the control group were obese, more likely to smoke, and had a higher number of comorbidities.

Overall, patients in the RA group received more antibiotic prescriptions than those in the control group; however, over 80% of the patient population had received a prescription within 10 years prior to the index date.

The most commonly prescribed antibiotics were penicillins (72%), followed by macrolides, trimethoprim, cephalosporins, tetracyclines, and quinolones (33%, 31%, 25%, 13%, and 13%, respectively).

Adjustments were made for confounding factors, and researchers found that the odds of antibiotic exposure were significantly higher in patients with RA compared with those without RA (odds ratio [OR], 1.60; 95% CI, 1.51-1.68). Redefining the index date based on first rheumatology referral did not change these results (OR, 1.68; 95% CI, 1.59-1.76).

Investigators identified a frequency-dependent relationship between the number of prescriptions and the odds of an RA diagnosis: with an increase in the number of unique antibiotic prescriptions, the magnitude of the association with RA also increased.

Researchers also found that antibiotic exposure timing was important, with higher odds of RA in patients who were exposed to antibiotics within 1 to 2 years prior to the index date (OR, 1.80; 95% CI, 1.70-1.90). Overall, clindamycin prescriptions were associated with the highest odds of developing RA.

Patients with RA were more likely to have a record of infection prior to RA diagnosis; therefore, the odds of RA were increased among those with a previous history of infection, ranging between 7% and 37%.

Prior to the index date, 7% and 14% of patients received at least 1 antiviral or antifungal medication. Adjustments were made for confounding factors, including antibiotic use; researchers found that both types of medications were associated with an increased risk for RA (OR, 1.19; 95% CI, 1.14-1.24 and OR, 1.27; 95% CI, 1.20-1.35, respectively).

Study limitations included the potential misclassification of RA cases, the possibility of protopathic bias based on the earliest recording of RA in patient medical history, and a potential underestimation of patient exposure to antibiotics.

“Studies of this nature, profiling a huge longitudinal population base, are critical for next stage detailed clinical studies and development of innovative therapies for this debilitating disease, including probing underlying mechanisms and potential associations between microbiota disturbances, infection, and RA onset,” the researchers concluded.


Sultan AA, Mallen C, Muller S, et al. Antibiotic use and the risk of rheumatoid arthritis: a population-based case-control study. BMC Med. 2019;17(1):154.