Skill Checkup: Suboptimally Treated Relapsing-Remitting Multiple Sclerosis (RRMS)

Christopher Luzzio, MD


January 26, 2022

A positive JCV antibody test in a patient with MS necessitates careful consideration of the risks and benefits of MS therapies. Individuals with MS and JCV antibodies have significant risk of developing PML while using natalizumab. This is particularly important for patients who are JCV antibody–positive while on therapy and who have been treated for more than 2 years or have had prior immunosuppressive treatment.

For patients who have or develop JCV antibodies while on DMT, available options include cladribine, an oral purine antimetabolite, and the immunomodulatory agent teriflunomide as alternatives to natalizumab.

Certain agents have not been associated with increased risk for PML; therefore, they may also be considered in this setting. These include the monoclonal antibodies alemtuzumab and usually ocrelizumab, and the sphingosine l-phosphate receptor modulators siponimod and ozanimod.

Although some cases of PML have occurred while using dimethyl fumarate and dimethyl fumarate and fingolimod, there have been far fewer than with natalizumab; therefore, those agents may still be used even when a patient has JCV antibodies. Because dimethyl fumarate may decrease lymphocyte counts, a complete blood cell count (CBC) should be done before starting therapy and annually to monitor lymphocyte counts. Fingolimod causes a dose-dependent lowering in peripheral lymphocyte count and thus may increase the risk for infection. Therefore, a CBC should be done before starting therapy with fingolimod.

The patient is already receiving the recommended dose of interferon beta-1b. Switching to a medication with a different mechanism of action or efficacy profile may be beneficial for this patient who has breakthrough disease activity.

Discontinuing DMT is not recommended for patients with stable MS.

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