Evaluation and prevention of infections associated with anti-B-cell agents used for treatment of non-malignant medical conditions

Medication	Effect on immune system	Associated infections^*	Pre-treatment testing^¶	Pre-treatment vaccinations^Δ	Comments
Rituximab	Induces apoptosis of CD20+ B cells leading to disruption of B and T cell interaction.	Bacterial: Tuberculosis and other mycobacterial infections Viral: HBV HCV EBV and CMV Herpes zoster virus COVID-19 (except belimumab) PML (JCV reactivation) (only rituximab) Fungal: Endemic mycoses Cryptococcal infection Pneumocystis pneumonia (only rituximab)^◊	Test for: TBI HBV HCV	Routine age-appropriate vaccinations Pneumococcal vaccine(s) RZV	Out of the mentioned anti-B cell therapies, rituximab is associated with the highest risk of serious infections. When administering vaccines during therapy, some experts choose to delay dosing of rituximab by 2 weeks after administration of a vaccine to optimize immunogenicity of the vaccine. Some experts choose to initiate Pneumocystis prophylaxis in patients taking rituximab monotherapy, although overall risk is low.
Ocrelizumab
Ofatumumab
Belimumab	Prevents stimulation of B cells but does not deplete them as the other agents do, leading to less risk of severe infection.				Belimumab is less likely to increase risk for serious infections compared with other anti B-cell agents.

This table serves as an overview of how to evaluate for and prevent infections in patients starting and/or taking anti-B-cell agents for treatment of non-malignant medical conditions. Infections highlighted in bold have been specifically associated with anti-B-cell agents and warrant extra consideration.

COVID-19: severe coronavirus disease 2019; CMV: cytomegalovirus; EBV: Epstein-Barr virus; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; JCV: John Cunningham virus; 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 pre-treatment 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 and for 6 to 12 months after cessation of therapy.

◊ Risk of pneumocystis pneumonia in patients taking rituximab for non-malignancy medical conditions is unclear. Pneumocystis pneumonia prophylaxis may be indicated when rituximab is used for certain conditions, such as vasculitis. Refer to UpToDate text on Pneumocystis pneumonia prophylaxis in patients without HIV for further details.

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Evaluation and prevention of infections associated with anti-B-cell agents used for treatment of non-malignant medical conditions