1. TB Screening traffic lights (before biologic drug therapy)
TB Screening traffic lights (before biologic drug therapy)
A quarter of the world’s population are estimated to be infected with latent (dormant) tuberculosis infection (LTBI) which may reactivate resulting in active TB disease.
Patients starting immunomodulatory/biologic therapy may be at increased risk of reactivation of latent TB.
These treatments modify the actions of the immune system which drive inflammation or disease progression but may also affect pathways that protect against infection. The risk of opportunistic infections will differ by agent and biological target.
We have adopted a ‘traffic light’ system to guide TB screening prior to initiation of immunomodulatory/biologic therapy.
- Patients who are prescribed a GREEN drug DO NOT require a TB screen
- Patients who are prescribed a RED or AMBER drug DO require a TB screen
These guidelines exclude cytotoxic chemotherapy. When prescribing cytotoxic chemotherapy please refer to the Electronic Medicines Compendium for TB screening requirements for individual agents.
Separate guidance exists for TB screening in solid organ transplantation and haematopoietic stem cell transplantation (HSCT).
The TB team are available for advice and should oversee TB preventative therapy.
Drug Traffic Lights for TB Risk
This list is dynamic. If any important omissions are noted, please contact us at antimicrobialpharmacist@ouh.nhs.uk
RED is higher risk for TB activation, AMBER moderate risk, GREEN low risk.
|
Therapeutic target |
Drug examples |
|
TNFα (monoclonal antibody) |
Adalimumab, certolizumab, pegol, golimumab, infliximab |
|
TNFα (soluble receptor) |
Etanercept |
|
IL-1 |
Anakinra, canakinumab |
|
Janus kinases |
Baricitinib, ruxolitinib, tofacitinib |
|
CD52 |
Alemtuzumab |
|
Purine analogue |
Cladribine |
|
IL-6 |
Tocilizumab, sarilumab |
|
IL-12/23 (common p40 subunit) |
Ustekinumab, guselkuman, tildrakizumab, risankizumab |
|
IL-17 |
Secukinumab, ixekizumab, brodalumab |
|
mTOR |
Everolimus, sirolimus, temsirolimus |
|
CD28 |
Abatercept |
|
CTLA-4 |
Ipilimumab |
|
PD-1 and PD-L1 |
Atezolizumab, nivolumab |
|
a4-integrins, LFA-1 |
Vedolizumab |
|
Sphingosine 1-phosphate receptor |
Fingolimod, siponimod fumaric acid, ponesimod, ozanimod |
|
Mitochondrial enzyme dihydroorotate dehydrogenase |
Leflunomide |
|
Teriflunomide |
|
|
IL-4 |
Dupilumab |
|
IL-5 |
Mepolizumab, reslizumab |
|
IgE |
Omalizumab |
|
Complement factor C5 |
Eculizumab |
|
VEGF |
Aflibercept, bevacizumab |
|
VEGFR |
Axitinib, cabozantinib, pazopanib |
|
EGFR |
Cetuximab, panitumumab |
|
ErbB2/HER2 |
Perztuzumab, trastuzumab |
|
ErbB receptor tyrosine kinases |
Afatinib, erlotinib, gefitinib, lapatinib |
|
BCR-ABL tyrosine kinase |
Bosutinib, dasatininib, imatinib, nilotinib |
|
BRAF/MEK kinases |
Cobimetinib, dabrafenib, trametinib |
|
Bruton tyrosine kinase (BTK) |
Ibrutinib |
|
PI3K |
Idelalisib |
|
Bcl-2 |
Ventetoclax |
|
CD19 |
Blinatumomab |
|
CD20 |
Rituximab, ofatumumab, ocrelizumab |
|
CD22 |
Epratuzumab, inotuzumab, ozogamicin |
|
CD30 |
Brentuximab vedotin |
|
CD33 |
Gemtuzumab, ozogamicin |
|
CD38 |
Daratumumab, Earatumumab |
|
CD319 (SLAMF7) |
Elotuzumab |
|
a4-integrins, LFA |
Natalizumab |
|
Proteosome |
Bortezomib, carfilzomib, ixazomib |
|
Non specific |
Dimethyl fumarate, diroximel fumarate |
|
Non specific |
Glatiramer acetate |
|
PDE 4 |
Apremilast |
|
Inosine monophosphate dehydrogenase |
Mycophenolate |
|
Non specific |
Ciclosporin |
|
Non specific |
Interferon beta |
|
Dihydrofolate reductase |
Methotrexate |
|
Non specific |
Azathioprine, 6-mercaptopurine |
Steroids and immunosuppressants such as methotrexate, mycophenolate, and cyclophosphamide do not require TB screening as routine. Further information about non-biologic immunosuppressant drugs and whether TB screening is required can be found in the Electronic Medicines Compendium (search for the drug, then under ‘clinical particulars’, and ‘special warnings and precautions for use’ - TB will be specifically listed if screening is required).
For bispecific or trispecific agents (e.g. teclistamab, epcoritamab) suggest adopting the risk rating of the highest rated agent and referring to the Electronic Medicines Compendium.
Latent TB Infection Screening (before biologic drug therapy)
References
- Alkadi A, Alduaji N, Alrehaily A. Risk of tuberculosis reactivation with rituximab therapy. Int J Health Sciences. 2017; 11(2): 41-44
- Bogas M, Machado P, Maurano AF, Costa L, Santos MJ, Fonseca JE et al. Methotrexate treatment in rheumatoid arthritis: management in clinical remission, common infection and tuberculosis. Results from a systematic literature review. Clin Rheumatol. 2010; 29(6): 629-635
- Bua A, Ruggeri M, Zanetti S, Molicotti P. Effect of teriflunomide on QuantiFERON-TB Gold results. Med Microbiol Immunol. 2017; 26: 73-75
- Clinical guideline: screening for latent TB infection prior to commencing biological therapy. University Hospitals Bristol NHS Foundation Trust; updated October 2018
- Clinical guideline: Tuberculosis (TB) screening prior to initiating targeted and biologic agents including anti-tumour necrosis factor (TNF) drugs; Frimley Health NHS Foundation Trust. January 2024
- Clinical guideline: Guideline for tuberculosis screening for biologic and immunomodulatory drugs for inflammatory conditions. Gloucestershire Hospitals NHS Foundation Trust; January 2023
- Clinical guideline: TB screening for targeted and biologic agents: Prescribing including Anti-Tumour Necrosis Factor Drugs; Imperial College Healthcare NHS Trust. September 2020
- Electronic Medicines Compendium (eMC). In: eMC. https://www.medicines.org.uk/emc. Accessed 1 May 2019
- Epstein DJ, Dunn J, Deresinski S. Infectious complications of multiple sclerosis therapies: implications for screening, prophylaxis and management. Open Forum Infect Dis. 2018; 5(8):ofy174
- Fernandez-Ruiz M, Meije Y, Manuel O, Akan H, Carratala J, Aguado JM, Delaloye J. ESCMID study group for infections in compromised hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (Introduction). Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2018; 24(Suppl 2): S2-9
- Moiola L, Barcella V, Benatti S, et al. The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement. Mult Scler. 2021; 27:331–346.
- Winkelmann A, Loebermann M, Reisinger EC, Hartung HP, Zettl UK. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol. 2016; 12(4): 217-33
- Martin L, Russell G (2021). ‘Anti-tumour necrosis alpha factor treatment, immunosuppression and chemotherapy prophylaxis’ in Kon OM (ed.) Tuberculosis in clinical practice. Switzerland: Springer Nature Switzerland AG, pp.311-326