Non-TNF-targeted drugs in rheumatic diseasescombined with latent tuberculosis infection

Rheumatic diseases(RD), a collection of autoimmune disorders affecting connective tissues, have a global prevalence of approximately 3%-5%. Characterized by immune-mediated attacks on the body's own tissues, these conditions lead to inflammation and tissue damage. Rheumatic disease patients frequently receive glucocorticoids, immunosuppressants, and biological agents, potentially elevating the risk of latent tuberculosis infection (LTBI) reactivation and Mycobacterium Tuberculosis (MTB) dissemination. Tumor necrosis factor-α(TNF-α)is crucial in immune responses, and TNF-targeted therapies could raise the risk of advancing from LTBI to active tuberculosis(TB). Compared to TNF inhibitors, non-TNF-targeted drugs-including IL-6, JAK, and B-cell inhibitors-pose a lower TB reactivation risk but may still modulate immune responses and defense against MTB. Our review synthesizes clinical research advancements in non-TNF-targeted therapies for rheumatic diseases, focusing on their association with TB reactivation risk. Non-TNF-targeted therapies demonstrate a reduced TB reactivation risk in rheumatic disease treatment, yet they necessitate rigorous TB screening and surveillance. Comprehensive infection status evaluation and prophylactic anti-tuberculosis treatment are essential for LTBI patients prior to therapy. The risk of TB infection is heightened in rheumatic disease patients undergoing biological therapy, particularly with TNF inhibitors. Despite the lower risk with non-TNF-targeted therapies, stringent screening and ongoing monitoring are imperative. Clinical practice should involve thorough patient assessment, personalized treatment planning, and preventive anti-tuberculosis strategies to balance therapeutic efficacy and infection risk. Further studies are warranted to elucidate the link between non-TNF-targeted therapies and TB risk and to refine treatment strategies for rheumatic diseases.This review seeks to investigate the potential TB reactivation risk associated with non-TNF-targeted therapies in rheumatic diseases and to offer theoretical foundations and novel perspectives for their clinical use.