The first case of progressive multifocal leukoencephalopathy (PML) has been reported in a patient with multiple sclerosis (MS) treated with fingolimod who had not also been treated with natalizumab, according to the FDA.
The patient was diagnosed with PML after almost eight months of treatment with fingolimod, a sphingosine 1-phosphate receptor modulator that was approved in 2010 for treating relapsing forms of MS.
The patient received one month of treatment with interferon beta-1a and azathioprine prior to beginning fingolimod. Those drugs were stopped when treatment with fingolimod began. However, the patient was also treated with “multiple courses” of IV corticosteroids for several months before and during treatment with fingolimod.
Treatment with fingolimod was discontinued after the diagnosis of PML, made on the basis of clinical symptoms and detection of JC viral DNA in CSF, according to the FDA statement, which does not say whether the patient survived. The case was reported in Europe.
After several PML cases were reported in patients with MS treated with natalizumab months after it was approved in 2004, it was taken off the market in 2005 and reintroduced in June 2006 with measures to address the risk of PML, including a restricted distribution program.
The FDA is working with Novartis, the drug’s manufacturer, to investigate this case and will make recommendations when the evaluation has been completed, the statement said. The FDA is advising patients not to stop treatment with fingolimod before discussing this with their health care professionals.
The precautions and warnings section of the fingolimod label includes a statement that the treatment causes a dose-dependent reduction in peripheral lymphocyte count due to reversible sequestration of lymphocytes in lymphoid tissues, and the drug “may therefore increase the risk of infections, some serious in nature,” but PML is not mentioned. The label also says that the drug has not been administered with antineoplastic, immunosuppressive, or immune-modulating therapies used to treat MS and that use of fingolimod with any of these treatments “would be expected to increase the risk of immunosuppression.”
Fingolimod was approved with a risk evaluation and mitigation strategy addressing the serious risks associated with treatment, including bradyarrhythmia and atrioventricular block at the start of treatment, infections, macular edema, respiratory effects, hepatic effects, and fetal risk.
—Elizabeth Mechcatie
IMNG Medical News