NEW ORLEANS—Now that testing for John Cunningham virus (JCV) antibody status is recommended for all patients with multiple sclerosis (MS) receiving infusions of natalizumab, the decision of whether to switch to another agent if the antibody status is positive might seem straightforward. However, the potential for relapsing and worsening MS might cause some patients to weigh the risks of natalizumab treatment, including progressive multifocal leukoencephalopathy (PML), a bit differently.
Researchers from Winthrop Comprehensive MS Care Center in Mineola, New York, presented findings from a study on patient decision-making and JCV antibody status at the 64th Annual Meeting of the American Academy of Neurology. Malcolm Gottesman, MD, and colleagues studied 71 patients who had initiated natalizumab therapy without knowing their JCV status. After antibody testing, patients were followed for six months and evaluated based on whether they elected to continue or discontinue natalizumab therapy. Of the 39 patients who were JCV negative, all continued on therapy and two (5%) experienced a relapse within the six-month period. Of the 32 patients who tested positive for JCV, nine elected to stop natalizumab therapy, but five patients (56%) had a relapse during the follow-up period. Of the 23 who continued, one patient (4%) relapsed. Of the nine patients who discontinued natalizumab after learning their JCV status, all but one (80%) resumed the treatment after they experienced an MS relapse.
In an interview with Neurology Reviews, coinvestigator Denise Cheng, RN, explained that personal acceptance of risk seemed to be the most relevant factor in patients’ decision of whether to stay on therapy after learning of a positive JCV assay. No other patient characteristics, such as age or gender, stood out among the groups. Although none of the patients treated at the clinic has developed a case of PML, Ms. Cheng advocated maintaining a close relationship with patients receiving infusions of natalizumab, as well as their families, to monitor for early signs that may indicate PML onset. Some of these signs, including cognitive, language, or visual impairment, are difficult to distinguish from MS symptoms.
As many as 50% to 70% of the population carries antibodies to JCV. The FDA confirmed in January 2012 that testing positive for anti-JCV antibodies has been identified as a risk factor for PML, stating, “The risks and benefits of continuing treatment [with natalizumab] should be carefully considered in patients who are found to be anti-JCV antibody positive and have one or more of the other known risk factors for PML.” The other two risk factors are treatment with natalizumab for more than two years and prior treatment with immunosuppressive medications. Prior immunosuppressive treatment has been shown to increase PML risk twofold to fourfold. People with all three known risk factors have an estimated risk of PML of 11 in 1,000 users.
Food and Drug Administration. Tysabri (natalizumab): Drug safety communication—New risk factor for progressive multifocal leukoencephalopathy (PML). January 20, 2012; http://www.fda.gov/Drugs/DrugSafety/ucm288186.htm.
Sorensen PS, Bertolotto A, Edan G, et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler. 2012;18(2):143-152.