TB Risk and Targeted Immunotherapy/Biologics Recommendations

Recommendations for TB Screening in Persons taking Targeted Immunotherapies (including Tumor Necrosis Factor Inhibitors)

San Francisco Department of Public Health (SFDPH) TB Clinic/UCSF Tuberculosis and Targeted Immunotherapy Group (TB-TIG)*

Updated March 2026

The use of new targeted immunotherapies (or biologics) has radically transformed the available treatment options for many diseases. These targeted immunotherapies work by blocking specific molecules that mediate certain immune responses or by depleting the cells that express them. Some can also increase the risk of progression to active TB disease by modulating the immunologic functions that contain TB organisms.

This risk varies by drug class and mechanism of action¹. The use of tumor necrosis factor (TNF)-alpha inhibitors has been associated with high risk of progression to active TB disease. Active TB disease occurring in the setting of TNF inhibitor use has a greater likelihood of involving extra-pulmonary sites or being disseminated at presentation². The risk has been reported to be greater with infliximab and adalimumab than with etanercept². Latent TB infection (LTBI) screening and treatment appears to significantly reduce the incidence of progression to active TB disease in these patients³.

There is growing evidence that other targeted immunotherapies (e.g., PD-1/PDL1 inhibitors, CTLA-4 inhibitors, JAK inhibitors, and IL-6 to name a few) are also associated with increased risk of TB reactivation. Data are rapidly emerging in this area and more targeted immunotherapies are approved each year.

The Table lists targeted immunotherapies as of March 2026 where 1) the manufacturer’s package insert recommends TB infection testing and/or 2) oncology guidelines from the National Comprehensive Cancer Network (NCCN) recommend TB infection testing (even if the manufacturer’s package insert does not)^4,5. SFDPH recommends TB screening in all targeted immunotherapies listed.

Based mostly on expert opinion, patients with a diagnosis of LTBI should be initiated on treatment for at least one month, if possible, prior to starting these targeted immunotherapies where a risk for TB progression has been identified.

Abbreviations (alphabetical): CD (cluster of differentiation), CTLA (cytotoxic T-lymphocyte-associated antigen 4), FLT (FMS-like tyrosine kinase), IL (interleukin), JAK (Janus kinase), mTOR (mammalian target of rapamycin), PD-1 (programmed cell death protein 1), PD-L1 (programmed death-ligand 1), TNF (tumor necrosis factor)

Notes:

# Brand names should be checked against the FDA Purple Book or Orange Book as this list will change with new drug approvals.

† Immune checkpoint inhibitors, including PD-1 (programmed cell death-1), PD-L1 (programmed cell death ligand-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA) inhibitors. While the manufacturer package inserts (i.e., FDA prescribing information) for PD-1 and PD-L1 inhibitors include statements about possible increased TB risk based on published animal (mice and macaque) studies, TB testing prior to use is not formally recommended^6-7. However, TB testing is recommended in NCCN guidelines⁵. In humans, meta-analysis and retrospective reviews of persons with cancer who received PD-1/PD-L1 inhibitors have identified an increased risk of TB disease^8-10. Currently SFDPH TB Clinic recommends TB testing prior to use of these drugs.

‡ Janus-associated kinase (JAK), IL-6 inhibitor and mTOR inhibitors: the manufacturer package inserts for some JAK inhibitors, IL-6 and mTOR inhibitors do not recommend TB infection screening prior to use, although they are included in the NCCN guidelines⁵. Increasing attention is focused on JAK inhibitors, which have broad immunomodulatory effects including on interferon-γ signaling that is critical for TB control. Currently SFDPH TB Clinic recommends TB testing prior to use of these drugs.

§ Interleukin (IL)-17 and IL-23 inhibitors: IL-17 and IL-23 inhibitors are approved in the U.S. for certain dermatology, rheumatology and gastroenterology conditions. The manufacturer package inserts for these drugs recommend TB testing prior to use. However, in early 2026 a Joint Position Statement from the National Psoriasis Foundation Medical Board and the International Psoriasis Council recommended against routine TB infection testing for individuals with psoriasis starting these therapies. This position statement was based on a review of clinical trial data, cohort studies, and post-marketing surveillance¹¹. These findings may not apply to persons with rheumatology and gastroenterology indications. More data is emerging -multiple in-vitro studies and a forthcoming study in non-human primates also suggest an association between IL-17 and IL-23 blockade and increased TB risk^12-15. Currently SFDPH TB Clinic recommends TB testing prior to use of these drugs.

*University of California, San Francisco, Tuberculosis and Targeted Immunotherapy Group (TB-TIG):

• Joel Ernst, MD, UCSF Division of Experimental Medicine
• Janice Louie, MD, MPH, SFDPH TB Clinic/ UCSF Division of Infectious Diseases
• Matthew Murrill, MD, PhD, UCSF Department of Medicine
• Allison Phillips, DNP, SFDPH TB Clinic
• Kyla Sherwood, MD, SFDPH TB Clinic
• John Szumowski, MD, MPH, UCSF Division of HIV, ID & Global Medicine
• Gustavo Velasquez, MD, MPH, UCSF Division of HIV, ID & Global Medicine

References:

1. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, Update February 2025. Available at URL: https://tbcontrollers.org/docs/NSTC/LTBI_Clinical_Guide_Feb2025_FINAL.pdf
2. Dixon WG, Hyrich KL, Watson KD, Lunt M, et al. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis. 2010;69(3):522.
3. Carmona L, Gómez-Reino JJ, Rodríguez-Valverde V, et al. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum. 2005;52(6):1766. 5
4. Murrill MT, Velásquez GE, Szumowski JD, et al. Tuberculosis Infection Screening Recommendations for Targeted Immunotherapies: Comparison of US Prescribing Information, Clinical Resources, and Quality Measures. Clin Infect Dis, 2025; ciaf628.
5. National Comprehensive Cancer Network. Prevention and Treatment of Cancer-Related Infections. Version 1.2026. Published March 11, 2026.
6. Lázár-Molnár E, Chen B, Sweeney KA, et al. Programmed death-1 (PD-1)-deficient mice are extraordinarily sensitive to tuberculosis. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13402-7.
7. Kauffman KD, Sakai S, Lora NE, et al. NIAID/DIR Tuberculosis Imaging Program; Sher A, Mayer-Barber KD, Andrade BB, Kabat J, Via LE, Barber DL. PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques. Sci Immunol. 2021 Jan 15;6(55):eabf3861.
8. Liu K, Wang D, Yao C, et al. Increased Tuberculosis Incidence Due to Immunotherapy Based on PD-1 and PD-L1 Blockade: A Systematic Review and Meta-Analysis. Front. Immunol. 2022; 13:727220.
9. Chen HW, Kuo YW, Chen, CY, et al. Increased Tuberculosis Reactivation Risk in Patients Receiving Immune Checkpoint Inhibitor-Based Therapy. The Oncologist 2024; 29: e498- e506.
10. Barber DL, Sakai S, Kudchadkar RR, et al. Tuberculosis following PD-1 blockade for cancer immunotherapy. Sci Transl Med. 2019 Jan 16;11(475):eaat2702.
11. Blauvelt A, Strober B, Eakin G, et al. Joint position statement from the National Psoriasis Foundation Medical Board and the International Psoriasis Council on routine testing for latent tuberculosis infection prior to and during treatment of psoriasis patients with interleukin 17 or interleukin 23 inhibitors. Journal of the American Academy of Dermatology, 2025; 94, 802-809.
12. Scriba TJ, Penn-Nicholson A, Shankar S, et al. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease. PLoS Pathog. 2017 Nov 16;13(11):e1006687.
13. Ogongo P, Tezera LB, Ardain A, et al. Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung. J Clin Invest. 2021 May 17;131(10):e142014.
14. Okamoto Yoshida Y, Umemura M, et al. Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung. J Immunol. 2010 Apr 15;184(8):4414-22. 15. Philippot Q, Ogishi M, Bohlen J, et al. Human IL-23 is essential for IFN-γ-dependent immunity to mycobacteria. Sci Immunol. 2023 Feb 17;8(80):eabq5204

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