RA-related factors may contribute to higher TB risk

Some factors associated with rheumatoid arthritis (RA), such as treatment with leflunomide, azathioprine, and prednisolone and concomitant obstructive lung disease, can elevate the risk of tuberculosis (TB) in biologic-naïve patients with RA, reveals a study.

“TB risk seems difficult to predict with precision in the individual biologic-naïve patient based on RA-associated risk factors,” the researchers said. “To further decrease the TB risk in patients with RA, we therefore suggest considering TB screening in biologic-naïve patients.”

A population-based case-control study using the Swedish Rheumatology Quality Register, the National Patient Register, and the Tuberculosis Register was conducted to identify RA patients with active TB and matched RA controls without TB between 2001–2014. The researchers obtained clinical data from medical records and estimated TB risk as adjusted odds ratio (AOR) with 95 percent confidence interval (CI) using univariate and multivariate logistic regression analyses.

Thirty-one RA patients with TB and 122 matched controls were included in the analyses following validation of diagnoses. All but three participants had reactivation of latent TB, of which the most prevalent was pulmonary TB (84 percent). [J Rheumatol 2021;48:1243-1250]

Ever use of methotrexate did not contribute to increased TB risk (AOR, 0.8, 95 percent CI, 0.3–2.0), but ever treatment with leflunomide (AOR, 6.0, 95 percent CI, 1.5–24.7), azathioprine (AOR, 3.8, 95 percent CI, 1.1–13.8), and prednisolone (AOR, 2.4, 95 percent CI, 1.0–6.0) did.

No significant differences were observed between maximum dose of prednisolone, treatment duration with prednisolone before TB, or cumulative dose of prednisolone the year before TB diagnosis between cases and controls.

Obstructive pulmonary disease also contributed to a heightened TB risk (AOR, 3.9, 95 percent CI, 1.5–10.7). Several mechanisms could help explain this association. For instance, immunological means such as dysregulation of phagocytes along with inhaled corticosteroid treatment could elevate the risk for mycobacterial infection. [Tuberculosis 2015;95:659-663; Am J Respir Crit Care Med 2011;183:675-678]

Malnutrition, a common problem in chronic obstructive pulmonary disease (COPD), could also contribute to increased TB risk. COPD and TB also had similar risk factors such as diabetes and tobacco smoking. [Tuberculosis 2015;95:659-663; Int J Chron Obstruct Pulmon Dis 2018;13:3307-3312; J Infect 2018;77:410-416; PLoS One 2019;14:e0214011; Tuberculosis 2014;94:544-550]

“Additionally, smoking (past or present) is common in patients with RA and has been identified as an independent risk factor for TB in these patients,” the researchers said. “We did not find an increased TB risk associated with smoking [in the present study], but due to missing data on smoking habits, especially among controls, this finding must be interpreted with caution.” [Open Access Rheumatol 2019;11:207-217; Arthritis Rheum 2006;55:19-26]

Moreover, epidemiological risk factors were noted in medical records typically at TB diagnosis for the cases. Apart from being born before 1950, half of RA patients with TB had reported risk factors that suggested previous TB exposure, according to the researchers.

The current study was limited by missing data in medical records, which was more common among controls than cases as regards epidemiological risk factors for TB. Data on socioeconomic factors were also sparse and thus not included in the analyses. In addition, the number of patients with some of the analysed exposures was low, making the results less robust and prone to bias.

“[T]hese patients might represent a cohort of RA patients with multicomorbidities with increased risk of TB,” the researchers said. “With few exposed individuals and risk of confounding factors, there is inherent uncertainty in the quantity and quality of these results and therefore should be cautiously interpreted.”