JCV detection in multiple sclerosis patients treated with natalizumab

Area of Science:

• Neurology
• Virology
• Immunology

Background:

• Natalizumab therapy increases the risk of progressive multifocal leukoencephalopathy (PML).
• Early identification of patients susceptible to PML is crucial due to the uniformly poor prognosis of established disease.
• Identifying subclinical viral infections may allow for intervention before clinical PML develops.

Purpose of the Study:

• To investigate if serial screening of plasma and cerebrospinal fluid (CSF) for polyomaviruses (JC virus [JCV] and BK virus [BKV]) can detect viral infection before clinical PML onset in natalizumab-treated patients.
• To assess the impact of treatment cessation on viral DNA levels.

Main Methods:

• Two hundred multiple sclerosis (MS) patients undergoing natalizumab treatment were screened for JCV and BKV DNA in CSF and plasma before treatment and every six treatments.
• Patients with detectable viral DNA had natalizumab treatment stopped, followed by clinical examinations and serial viral DNA testing until normalization.

Main Results:

• No patient developed clinical evidence of PML during the study.
• Eight out of 200 patients (4%) had detectable JCV or BKV DNA.
• Five patients tested positive for BKV DNA in CSF, and three patients tested positive for JCV DNA (one in plasma, two in CSF).
• Following natalizumab cessation, all patients showed undetectable viral DNA levels.

Conclusions:

• Serial CSF screening for JCV in natalizumab-treated patients can identify individuals at heightened risk for PML.
• Discontinuing natalizumab treatment upon detection of viral DNA may prevent the clinical development of PML.
• This screening strategy offers a potential method for risk stratification and early intervention in natalizumab-treated patients.