For the first time, progressive multifocal leukoencephalopathy (PML) has been reported in patients with multiple sclerosis (MS) treated with fingolimod who had not previously been treated with an immunosuppressant, according to an FDA warning issued on August 4.
The FDA described two cases of PML—one is considered definite and the second is considered probable—in patients who had not received prior treatment with an immunosupressant drug for MS or any other medical condition. Prior cases of PML in patients taking fingolimod, including a case in a European patient in 2013, were confounded by immunosuppressant use before or concurrent with the drug.
In addition, Novartis, the manufacturer of the drug, reported on August 17 that it had been informed of another case of PML in a patient who did not have prior exposure to natalizumab. This patient has a history of colorectal cancer that was treated with chemotherapy and radiation treatment, and Crohn’s disease.
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. People on fingolimod should 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,” said the agency.
Symptoms in the patient with definite PML, a 54-year-old who had had MS for about 14 years and had been treated with fingolimod for about 2.5 years, included instability while walking, clumsiness, inattention, somnolence, and mental sluggishness. John Cunningham virus (JCV) DNA was present in the patient’s CSF, and MRI findings were characteristic of PML. The probable case was in a 49-year-old who had been treated with fingolimod for about four years and had no symptoms, but had new MRI lesions consistent with PML and a CSF test that was positive for JCV DNA.
Fingolimod, taken once per day by mouth, is a sphingosine 1-phosphate receptor modulator marketed by Novartis as Gilenya. 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 cases of PML. Possible cases of PML associated with fingolimod should be reported to the FDA’s MedWatch program website or by calling 1-800-332-1088.
—Elizabeth Mechcatie