Evaluation and prevention of infections associated with anti-integrin monoclonal antibodies (mAbs) and S1P receptor modulators

Medication	Effect on immune system	Associated infections^*	Pre-treatment testing^¶	Pre-treatment vaccinations^Δ	Comments
Anti-integrin monoclonal antibody
Vedolizumab	Inhibits alpha-4-beta-7 integrin and prevents its binding to MAdCAM-1, leading to impaired migration of memory T cells to the gut mucosal endothelium.	Bacterial: Tuberculosis and other mycobacterial infections Viral: EBV and CMV PML (JCV reactivation)	Test for: TBI	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV	Vedolizumab does not appear to reduce parenterally delivered vaccine responses, but the response to oral vaccines may be lower.
Natalizumab	Inhibits alpha-4-beta-1 integrins, preventing it from binding to VCAM, leading to the inhibition of leukocyte migration to site of infection (including the CNS).	Bacterial: Tuberculosis and other mycobacterial infections Viral: PML (JCV reactivation) HBV HCV EBV and CMV Herpes zoster virus and HSV Fungal: Cryptococcal infection Aspergillosis	Test for: TBI HBV HCV JCV^◊	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV	Live vaccines should not be administered during the course of treatment nor up to 4 months after stopping therapy.
Sphingosine-1-phosphate (S1P) receptor modulator
Fingolimod^§	Inhibits S1P and prevents T cell migration from lymph nodes.	Bacterial: Tuberculosis and other mycobacterial infections Viral: Herpes zoster virus HSV PML Human herpesvirus 8-associated tumors Fungal: Cryptococcal infection	Test for^¥: TBI HBV HCV	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV	Fingolimod should not be used with natalizumab due to increased risk of PML.

This table serves as an overview of how to evaluate for and prevent infections in patients starting and/or taking anti-integrin monoclonal antibodies and S1P receptor modulators. Infections highlighted in bold have been specifically associated with the biologic agent and warrant extra consideration.

CMV: cytomegalovirus; CNS: central nervous system; EBV: Epstein-Barr virus; HBV: hepatitis B virus; HCV: hepatitis C virus; HHV-8: human herpesvirus 8; HIV: human immunodeficiency virus; HSV: herpes simplex virus; JCV: John Cunningham virus; LTBI: latent tuberculosis infection; MAdCAM-1: mucosal vascular addressin cell adhesion molecule 1; PML: progressive multifocal leukoencephalopathy; RZV: recombinant (non-live) zoster vaccine (Shingrix); S1P: sphingosine-1-phosphate; TBI: tuberculosis infection; VCAM: vascular cell adhesion protein.

* 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.

◊ We also obtain baseline magnetic resonance imaging of the brain prior to initiating therapy with natalizumab.

§ Other S1P receptor modulators (eg, siponimod, ozanimod) should be managed like fingolimod.

¥ Some clinicians opt to test for JCV similar to the approach used for patients starting natalizumab; however, this is not routine among all clinicians.

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Evaluation and prevention of infections associated with anti-integrin monoclonal antibodies (mAbs) and S1P receptor modulators