Is Varicella Zoster Virus (VZV) antibody Immunoglobulin G (IgG) indicated for screening in Multiple Sclerosis (MS) to initiate therapy?

From the Guidelines

No, Varicella Zoster Virus (VZV) antibody IgG testing is not specifically indicated in screening for multiple sclerosis (MS) prior to starting therapy. VZV antibody testing is primarily used to determine immunity to chickenpox or to diagnose VZV infections. However, VZV antibody testing may be relevant before starting certain MS therapies, particularly immunosuppressive medications like fingolimod, ocrelizumab, or natalizumab, as these can increase the risk of VZV reactivation (shingles) 1. In these cases, checking VZV immunity status helps determine if vaccination is needed before immunosuppressive therapy begins. If a patient is found to be non-immune to VZV, vaccination should be completed at least 4-6 weeks before starting immunosuppressive therapy. This approach is part of a broader pre-treatment screening that typically includes tests for tuberculosis, hepatitis B and C, and HIV, rather than being specific to MS diagnosis or general treatment initiation.

The provided evidence does not directly support the use of VZV antibody IgG testing in screening for MS prior to starting therapy. The studies focus on the management of patients with multiple myeloma receiving bispecific antibody therapy 1, the use of MRI in multiple sclerosis 1, and the stratification and monitoring of natalizumab-associated progressive multifocal leukoencephalopathy risk 1. However, the most recent and highest quality study 1 provides guidance on the management of infections in patients with multiple myeloma receiving bispecific antibody therapy, which may be relevant to the management of patients with MS receiving immunosuppressive therapies.

Key points to consider:

• VZV antibody testing is not specifically indicated in screening for MS prior to starting therapy.
• VZV antibody testing may be relevant before starting certain MS therapies, particularly immunosuppressive medications.
• Checking VZV immunity status helps determine if vaccination is needed before immunosuppressive therapy begins.
• Vaccination should be completed at least 4-6 weeks before starting immunosuppressive therapy if a patient is found to be non-immune to VZV.

From the FDA Drug Label

Varicella Zoster Virus Antibody Testing/Vaccination Patients without a healthcare professional confirmed history of chickenpox or without documentation of a full course of vaccination against VZV should be tested for antibodies to VZV before initiating fingolimod VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with fingolimod, following which initiation of treatment with fingolimod should be postponed for 1 month to allow the full effect of vaccination to occur

The VARICELLA ZOSTER VIRUS ANTIBODY IgG is indicated for screening patients for immunity to varicella zoster virus before starting therapy with fingolimod for Multiple Sclerosis (MS), but it is not directly indicated for screening for MS itself. The purpose of the screening is to determine if the patient needs to be vaccinated against varicella zoster virus before starting fingolimod treatment. 2

From the Research

Varicella Zoster Virus Antibody IgG in MS Screening

• The presence of Varicella Zoster Virus (VZV) antibody IgG has been studied in the context of multiple sclerosis (MS) to understand its potential role in the disease process and as a marker for therapy initiation 3, 4, 5, 6, 7.
• Research has shown that VZV antibody IgG can be detected in the cerebrospinal fluid (CSF) of MS patients, indicating intrathecal synthesis of these antibodies 4, 5.
• A study published in 2009 found that IgG antibodies against measles, rubella, and VZV can predict conversion to MS in patients with clinically isolated syndrome (CIS) 5.
• Another study from 2012 correlated measles IgG antibody index with T2 lesion load on MRI in patients with early MS, suggesting a potential prognostic impact of MRZ reaction (MRZR) on disease activity 6.
• However, an earlier study from 1982 found that electrofocused "bands" of oligoclonal CSF IgG do not carry antibody activity against measles, VZV, or rotaviruses, indicating that the intrathecally synthesized viral antibodies are not carried by the oligoclonal bands of CSF IgG 7.

Implications for MS Therapy

• The detection of VZV antibody IgG in MS patients may have implications for therapy initiation, as it could potentially serve as a marker for disease activity or progression 5, 6.
• However, more research is needed to fully understand the role of VZV antibody IgG in MS and its potential as a therapeutic target 3, 4, 7.
• The studies suggest that VZV antibody IgG may be a useful tool in the diagnosis and monitoring of MS, particularly when used in combination with other markers such as MRI findings 5, 6.