medwireNews: Exposure to systemic oral antibiotics is associated with a higher risk for rheumatoid arthritis (RA), a database analysis suggests.
Based on their findings, Lindsay Hall (Quadram Institute Bioscience, Norwich, UK) and colleagues report “a strong association between antibiotic usage and the onset of RA,” while acknowledging that “there remain many unanswered questions, particularly whether this is related to infections themselves, alterations in the microbiota, or a combination of the two.”
They identified 22,677 RA patients from the Clinical Practice Research Datalink, who were each matched to up to five controls (90,013 in total) based on year of birth, sex, and general practice.
As reported in BMC Medicine, individuals with RA were 1.6 times more likely to have been exposed to antibiotics over a median of 10 years prior to diagnosis than those without RA.
The researchers note that the odds remained the same when they based the index date on first referral to a rheumatologist in order to rule out the potential that early RA symptoms (experienced prior to diagnosis) may have triggered the need for antibiotic treatment.
The results also highlight that the odds of developing RA rose in line with an increasing number of antibiotic prescriptions, and the strength of this frequency-dependent relationship was affected by the timing of antibiotic exposure. RA onset was more likely to occur in individuals exposed to antibiotics 1–2 years before the index date (odds ratio [OR]=1.80) compared with those exposed 5–10 years before the index date (OR=1.57).
All antibiotics included in this study (eg, penicillins, macrolides, and quinolones) were associated with an increased incidence of RA. However, the investigators observe that the odds of developing RA varied depending on the mode of action of the antibiotics; bactericidal antibiotics (OR=1.45) showed a stronger relationship than bacteriostatic antibiotics (OR=1.31), for instance.
The type of infection also proved to be important, with respiratory infections associated most strongly with RA, in particular, upper respiratory tract (URT) infections. Specifically, only antibiotic-treated cases of URT infections were strongly associated with RA, with no association observed for untreated URT infections, which supports previous research in patients with juvenile idiopathic arthritis.
"[A]ssociated antibiotic usage is likely to be the main associative factor for the increased incidence of RA in this cohort,” say the researchers.
Although they conclude that “antibiotic prescriptions are associated with a higher risk of RA,” the researchers emphasize that “it is currently unclear if the major driver is infection and/or antibiotic usage; therefore, these observations require extensive additional studies (both case-controlled and mechanistic) to determine direct causation.”
By Hannah Kitt
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