Evaluation and prevention of infections associated with TNF-alpha inhibitors (TNFi), abatacept, and janus kinase (JAK) inhibitors

Medication	Effect on immune system	Associated infections^*	Pre-treatment testing^¶	Pre-treatment vaccinations^Δ
TNFi
Infliximab	Inhibits macrophage activation and granuloma formation and function	Bacterial: Tuberculosis^◊ and other mycobacterial infections Listeria monocytogenes Nocardia spp. Legionella spp. Viral: HBV HCV Herpes zoster virus Fungal: Endemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis, paracoccidioidomycosis, talaromycosis) Candidal infections Cryptococcal infection Aspergillosis Parasitic: Toxoplasma gondii (rare)	Test for: TBI HBV HCV In endemic regions, obtain history of possible recent (eg, in the last two years) infection with endemic fungi. If history is concerning, obtain a chest radiograph. In coccidioidomycosis-endemic regions, obtain Coccidioides serology	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV
Etanercept^◊
Adalimumab
Certolizumab pegol
Golimumab
Anti-T cell agents
Abatacept	Inhibits CD80/CD86, thus preventing suppression of regulatory T cell activity	Bacterial: Tuberculosis and other mycobacterial infections Viral: Hepatitis B virus Hepatitis C virus EBV and CMV	Test for: TBI HBV HCV	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV
Janus Kinase (JAK) inhibitors
Ruxolitinib	Inhibits JAK signaling and disrupts signaling pathways involved in immune cell (eg, NK cells, macrophages, T cells) activation and migration	Bacterial: Tuberculosis and other mycobacterial infections Viral: Hepatitis B virus Hepatitis C virus EBV and CMV Herpes zoster virus PML (JCV reactivation) Fungal: Endemic mycoses Cryptococcal infection Pneumocystis pneumonia	Test for: TBI HBV HCV In coccidioidomycosis-endemic regions, obtain Coccidioides serology (only ruxolitinib)	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV
Tofacitinib
Baricitinib
Other (upadacitinib, filgotinib, peficitinib, abrocitinib)

This table serves as a comprehensive review of how to evaluate for and prevent infections in patients starting and/or taking TNFi, abatacept, or JAK inhibitors. Infections highlighted in bold have been specifically associated with the biologic agent and warrant extra consideration.

CMV: cytomegalovirus; EBV: Epstein-Barr virus; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; JCV: John Cunningham virus; NK cells: natural killer cells; PML: progressive multifocal leukoencephalopathy; RZV: recombinant (non-live) zoster vaccine (Shingrix); TBI: tuberculosis infection.

* In addition to the infections listed, typical, common bacterial, and viral infections should also be considered in the differential when infection is suspected in a patient taking the specified agent.

¶ For patients who do not have a negative HIV test documented in their records or are at increased risk of acquiring HIV (eg, men who have sex with men, engagement in sex work), the pretreatment infectious testing process is a good opportunity to provide routine HIV screening prior to the initiation of immunosuppression. Treat any infections found on pre-treatment testing. Control of infection should be demonstrated prior to initiating immunosuppressive therapy.

Δ Live and non-live vaccines should be administered no later than 4 and 2 weeks, respectively, prior to initiating therapy. Vaccine responses may be attenuated while on therapy.

◊ Etanercept is associated with a lower risk of tuberculosis (TB) compared to the other TNFi.

Graphic 143349 Version 1.0

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Evaluation and prevention of infections associated with TNF-alpha inhibitors (TNFi), abatacept, and janus kinase (JAK) inhibitors