Fast Five Quiz: Relapsing-Remitting Multiple Sclerosis Management

Christopher Luzzio, MD; Kerstin Hellwig, MD


June 30, 2022

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the brain that can lead to severe disability or death. Natalizumab has been associated with PML. Risk factors for PML are previous immunosuppression, duration of exposure to natalizumab beyond 2 years, and JC virus antibody positivity.

Natalizumab was voluntarily and temporarily withdrawn from the market in 2005 owing to its association with three cases of PML. However, the FDA reapproved it in 2006 under a special restricted distribution program known as TYSABRI Outreach: Unified Commitment to Health (TOUCH).

The AAN guidelines advise that treatment with natalizumab may be initiated in patients with MS with positive anti-JCV antibody indexes above 0.9 only when there is a reasonable chance of benefit compared with the low but serious risk for PML. Patients may consider natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate in the context of the PML risk associated with these agents. Patients taking natalizumab who are or become JCV antibody–positive, especially with an index of above 0.9 while on therapy, should consider switching to a DMT with a lower PML risk.

Similarly, European guidelines recommend monitoring treatment safety with DMTs, a standardized reference brain MRI scan should be performed every year in low-risk PML patients and more frequently (every 3-6 months) in high-risk PML patients (JCV-positive, natalizumab treatment for longer than 18 months).

Fingolimod is associated with macular edema, pulmonary dysfunction, and cardiac adverse effects. Teriflunomide is associated with alopecia.

Learn more about the treatment and management of MS.


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