BACKGROUNDBiological therapies and Janus kinase (JAK) inhibitors have revolutionised the management of immune-mediated and oncologic diseases, but concerns remain regarding their potential to increase TB risk.OBJECTIVETo systematically synthesise evidence from previous systematic reviews on the risk of TB disease associated with different biological classes and JAK inhibitors.METHODSFollowing Preferred Reporting Items for Overviews of Reviews guidelines, we conducted an umbrella review of systematic reviews and meta-analyses, registered in PROSPERO (CRD42024497515). Twenty-five reviews met the inclusion criteria. Data were extracted on TB incidence, risk estimates, type, and time to onset. Risk of bias was assessed using ROBIS.RESULTSAnti-TNF monoclonal antibodies (infliximab, adalimumab) were consistently associated with the highest TB risk (odds ratio commonly 3-5), with greater proportions of disseminated/extra-pulmonary disease compared to etanercept. Combination immunosuppression further increased risk. IL-6, IL-17, and IL-23 inhibitors showed low TB reactivation rates under screening and prophylaxis protocols. JAK inhibitors (notably tofacitinib) conferred geographically variable risk, higher in intermediate/high-burden countries. Immune checkpoint inhibitors, especially PD-1/PD-L1 agents, were linked to TB incidence far above background rates.CONCLUSIONTB risk varies markedly across biologic and targeted agents. Risk-based TB infection screening and tailored prophylaxis beyond anti-TNF therapy are warranted, particularly in endemic regions..
Alves et al. (Mon,) studied this question.