For the first time, progressive multifocal leukoencephalopathy has been reported in patients with multiple sclerosis who are being treated with fingolimod but have not been treated with an immunosuppressant, according to a Food and Drug Administration warning issued on Aug. 4.
Two cases have been reported; one is a definite case and the second is considered a probable case. A European case of progressive multifocal leukoencephalopathy (PML) in a patient on fingolimod previously described by the FDA in 2013 was not “conclusively linked” to the drug because the patient had been treated with an immunosuppressant drug that can cause PML and had been treated with intravenous corticosteroids during treatment with fingolimod, the statement said.
PML is a rare, serious, potentially fatal brain infection caused by the JC (John Cunningham) virus, which is present in most people, but can cause PML in patients who are immunosuppressed or are on immunosuppressive drugs. Symptoms of PML may include clumsiness of limbs, progressive weakness on one side of the body, confusion, vision disturbances, as well as changes in thinking, memory, and orientation. Clinicians who suspect that a patient on fingolimod may have PML should stop treatment and evaluate the patient for a diagnosis of PML, according to the FDA warning, which advises people on fingolimod to contact their health care professionals immediately “if they experience symptoms such as new or worsening weakness; increased trouble using their arms or legs; or changes in thinking, eyesight, strength, or balance.”
Symptoms in the patient with definite PML, a 54-year old who had had MS for 13-14 years and had been treated with fingolimod for about 2.5 years, included instability while walking, clumsiness, inattention, somnolence, and mental sluggishness. JC viral DNA was present in the cerebrospinal fluid and MRI findings were characteristic of PML. The probable case was in a 49-year-old who had been treated with fingolimod for about 4 years, and had no symptoms, but had new MRI lesions consistent with PML and a CSF test that was positive for JC viral DNA.
To diagnose PML, “an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended,” according to the prescribing information for natalizumab (Tysabri), an intravenously administered treatment for MS that increases the risk of PML.
Fingolimod, taken once a day by mouth, is a sphingosine 1-phosphate receptor modulator marketed as Gilenya by Novartis. It was approved in 2010 and is indicated for treating relapsing forms of MS to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.
The fingolimod prescribing information and Medication Guide are being updated to include information about the two cases.
Possible cases of PML associated with fingolimod should be reported to the FDA’s MedWatch program website or by calling 1-800-332-1088.
