Evaluation and prevention of infections associated with IL-1, IL-6, IL-17, and IL-12/23 inhibitors

Medication	Effect on immune system	Associated infections^*	Pre-treatment testing^¶	Pre-treatment vaccinations^Δ	Comments
IL-1 inhibitors
Anakinra	Inhibits IL-1 and prevents activation of proinflammatory cytokine pathways	Bacterial: Tuberculosis and other mycobacterial infections Viral: HBV HCV Herpes zoster virus Fungal: Candidal infections Cryptococcal infection Aspergillosis	Test for: TBI HBV HCV	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV	Risk of infections with IL-1 inhibitors is lower than with other biologic agents Can be a useful treatment option while investigation for occult infection is ongoing
Canakinumab
Rilonacept
IL-6 inhibitors
Sarilumab	Inhibits IL-6 and prevents proinflammatory cytokine release	Bacterial: Tuberculosis and other mycobacterial infections Viral: HBV HCV Herpes zoster virus Fungal: Candidal infections Pneumocystis pneumonia	Test for: TBI HBV HCV	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV
Tocilizumab
IL-17 inhibitors
Secukinumab (IL-17)	Inhibits IL-17 and prevents release of proinflammatory cytokines	Bacterial: Tuberculosis and other mycobacterial infections Fungal: Candidal infections Dermatologic fungal infections (eg, tinea)	Test for: TBI	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV
Ixekizumab (IL-17)
Brodalumab (IL-17) Bimekizumab (IL-17)
IL-12 and IL-23 inhibitors
Ustekinumab (IL-12, IL-23)	Inhibits IL-12 and IL23 and interferes with NK cell activation and CD4 T cell differentiation	Fungal: Candidal infections Dermatologic fungal infections (eg, tinea)	Test for:^◊ TBI HBV HCV	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV
Guselkumab (IL-23)	Inhibits IL-23 and prevents proinflammatory cytokine release
Risankizumab (IL-23)	Binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor	Bacterial: Tuberculosis and other mycobacterial infections Fungal: Candidal infections Dermatologic fungal infections (eg, tinea)	Test for:^§ TB

This table serves as an overview of how to evaluate for and prevent infections in patients starting and/or taking IL-1, IL-6, IL-17, or IL-12/23 inhibitors.

HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; IL: interleukin; NK cells: natural killer cells; RZV: recombinant (non-live) zoster vaccine (Shingrix); TBI: latent 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 pre-treatment infectious testing process is a good opportunity to provide routine HIV screening prior to the initiation of immunosuppression. Treat any latent or active 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.

◊ Although the drug labels for these agents warns that the risk of TBI and HBV reactivation may be increased, post-marketing data has not shown a significantly increased risk of infection with these agents. Nevertheless, we continue to test for these infections because the benefit of testing outweighs the harms.

§ Risankizumab (an IL-23 inhibitor) appears to have a lower risk for HBV and HCV reactivation compared with guselkumab or ustekinumab, thus we do not test for HBV or HCV in patients starting risankizumab.

Graphic 143347 Version 1.0

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Evaluation and prevention of infections associated with IL-1, IL-6, IL-17, and IL-12/23 inhibitors