Impact of seropositivity and disease-modifying antirheumatic drugs on pulmonary tuberculosis risk in rheumatoid arthritis

Background It remains unclear whether active pulmonary tuberculosis risk is still high in rheumatoid arthritis patients in settings where tuberculosis infection screening is performed before the use of biologicals. Moreover, the impacts of seropositivity and disease-modifying antirheumatic drugs on active pulmonary tuberculosis risk should be elucidated. Methods The incidence of active pulmonary tuberculosis was compared between patients with rheumatoid arthritis (n=59 577; 41 501 seropositive rheumatoid arthritis and 18 076 seronegative rheumatoid arthritis) and 1:5 age-and sex-matched controls without rheumatoid arthritis (n=297 885) enrolled between 2010 and 2017. The participants were followed until December 2019. Results During a median follow-up duration of 4.4 years after a 1-year lag period (interquartile range 2.6–6.4 years; maximum 9 years), patients with rheumatoid arthritis showed a 3.2-fold (95% CI 2.91–3.55) higher active pulmonary tuberculosis risk than matched controls, even after adjusting for potential confounders. In an analysis of rheumatoid arthritis serological status, patients with seropositive rheumatoid arthritis and those with seronegative rheumatoid arthritis showed 3.20-fold (95% CI 2.86–3.58) and 2.54-fold (95% CI 2.13–3.04) increased risks, respectively, relative to matched controls. Furthermore, rheumatoid arthritis patients who were exposed to biological or targeted synthetic and disease-modifying antirheumatic drugs and those not exposed to the drugs showed 4.68-fold (95% CI 3.69–5.93) and 2.88-fold (95% CI 2.59–3.20) increased risks, respectively, relative to matched controls. In rheumatoid arthritis patients, active pulmonary tuberculosis risk factors included male sex, underweight and comorbidities such as diabetes mellitus. Conclusion Rheumatoid arthritis patients are prone to active pulmonary tuberculosis development, with rates affected by seropositivity and disease-modifying antirheumatic drugs. Focused tuberculosis screenings may need to be carried out in rheumatoid arthritis patients based on our results.