Analysis: IL-17, JAK Inhibitors May Carry Elevated Risk for TB
Key Takeaways
A new analysis of TriNetX data suggests increased risk for tuberculosis (TB) among all evaluated immunosuppressants except IL-4/13 inhibitors.
TNF-α inhibitors showed the highest TB incidence rate; IL-23 and JAK inhibitors also showed elevated risks.
The authors said the findings show the need for routine TB surveillance in patients treated with immunosupressants.
A large population-based analysis using data from TriNetX suggests a elevated risk of active tuberculosis (TB) in patients treated with systemic immunosuppressive therapies (including IL-17, IL-23, IL-12/23, Janus kinase (JAK) inhibitors), cyclosporine, and tumor necrosis factor (TNF)-α inhibitors.
Researchers evaluated data from over 135 million patients between 2004 and 2024 treated with these agents for any indication and maintained therapy for at least 1 year were included. The primary endpi incidence of active TB (ICD-10 A15–A19) within 1 year of drug initiation. Individuals with latent TB infection or exposure to multiple study drugs were excluded.
According to the data, all drug classes (except dupilumab) were associated with elevated TB rates compared with the general population TB incidence of 28.6 cases per 100,000 exposure-years. Adjusted odds ratios for TB ranged from 2.4 with IL-12/23 inhibitors to 5.5 with TNF-α inhibitors (all P < 0.0001). Sensitivity analyses excluding international patients upheld the findings.
Hazard ratios compared with TNF-α inhibitors were lower for dupilumab (HR 0.18, P < 0.001) and cyclosporine (HR 0.54, P < 0.001) after adjustment for TB risk factors like HIV, diabetes, malnutrition, and others.
The study authors note that newer immunomodulators are also associated with meaningful increases in TB risk. Re-screening rates at one year were low (4% for IL-4/13 users and 20–31% for other drugs).
"Our results support routine TB screening and surveillance for IL-12/23 inhibitors, IL-23 inhibitors, IL-17 inhibitors, JAK inhibitors, cyclosporine, and TNF-α inhibitors," the authors wrote. "Given the drug-associated twofold-to-fivefold increase in TB over the population risk, surveillance strategies should be standardized, though we lack cost information to determine cost-effectiveness."
Source: Woodie BR, et al. J Am Acad Dermatol. Published online September 2025. doi:10.1016/j.jaad.2025.09.021