Clinical Management of High-Risk Patients with Relapsing-Remitting Multiple Sclerosis (MS) Treated with Natalizumab

Background: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system that mainly occurs in the setting of immunosuppression. Natalizumab is an immunomodulatory agent indicated for the treatment of relapsing-remitting MS that is most often associated with the development of PML. There are three predictive risk factors for developing natalizumab-associated PML: JC virus (JCV) antibody status, history of immunosuppressant therapy, and duration of natalizumab treatment. The estimated risk of a JCV-positive person exposed to natalizumab for 25-48 months with no prior immunosuppressant use is 5/1000 and for those previously exposed to immunosuppressant use is 11/1000.  Clinical management considerations in high-risk patients with two or more risk factors are important in the overall scope of treatment outcomes.

Objectives: To describe the clinical management of high-risk patients with relapsing-remitting MS treated with natalizumab who have two or more risk factors.

Methods: We review patient charts for 210 relapsing-remitting MS patients actively treated with natalizumab in our clinic. 

Results: Among the 210 patients, 27 patients have at least two risk factors; tested JCV-positive and were exposed to natalizumab for over 25 months. In addition, 5 of the 27 patients have all three risk factors, which includes prior exposure to immunosuppressant. According to our protocol, all MS patients actively treated with natalizumab are tested for the JCV twice a year. In addition, physicians clinically monitor high-risk patients with two or more risk factors every 6 months with MRI and scheduled office visits. All 27 patients are currently stable and no confirmed cases of PML have been reported. 

Conclusions: Our experience indicates that a small population of high-risk relapsing-remitting MS patients treated with natalizumab may be managed and monitored safely and effectively. The Food and Drug Administration (FDA) designates a black box warning regarding natalizumab increasing the risk of PML; therefore, the potential risks and benefits must be carefully assessed prior to maintaining high-risk patients on natalizumab therapy.