Complications from Gilenya Treatment Managed Successfully, Case Report Says

A case study reported the successful management of a multiple sclerosis (MS) patient who developed a rare condition in the brain — progressive multifocal leukoencephalopathy (PML) — due to treatment with Novartis Pharmaceutical’s Gilenya (fingolimod).

The study, titled “Fingolimod-associated PML with mild IRIS in MS: A clinicopathologic study,” was published in the journal Neurology Neuroimmunology & Neuroinflammation.

The patient was a 34-year-old woman whose MS was diagnosed at age 14. She had been treated with interferon-beta 1b for 11 years and experienced 12 MS relapses during that period. Interferon treatment was discontinued.

For the past four years she had been taking Gilenya without experiencing any relapses and no signs of disease worsening.

The woman visited the clinic because she noticed muscle weakness in her right hand, dysarthria (which involves slurred or slow speech), and hemiparetic gait (abnormal gait caused by weakness in the muscles on one side of the body).

Gilenya treatment was discontinued because the patient had low numbers of white blood cells in her circulation.

One month later, she was admitted to the hospital. Aphasia (impairment of language, affecting the production or comprehension of speech and the ability to read or write) and right hemiplegia (paralysis of one side of the body) worsened during the first month of hospitalization.

A very low level of JC virus was detected in the patient’s cerebrospinal fluid, which bathes the brain and the spinal cord. Infection with JC virus can cause PML, with symptoms including mental deterioration, vision loss, speech disturbances, ataxia (inability to coordinate movements), paralysis, and coma.

A biopsy of her brain tissue showed there were signs of JC virus infection and a mild immune response to it, suggesting a diagnosis of PML-immune reconstitution inflammatory syndrome (PML-IRIS). IRIS is an exacerbated inflammatory response that aggravates the damage caused by JC virus infection.

The patient was treated with 1 gram of methylprednisolone (intravenously) daily for three days, and weekly oral mefloquine. Two months later, no JC virus could be detected in her cerebrospinal fluid, and her white blood cell counts returned to normal. Aphasia and right hemiplegia gradually improved.

The researchers emphasized there have only been a total of 13 cases of PML reported in Gilenya-treated patients with relapsing-remitting MS to date, including this single case of PML-IRIS. The team highlights that Gilenya-associated PML in MS may be accompanied with IRIS, but that it may be difficult to detect because the symptoms are relatively mild,  causing underestimation.

“The clinical and pathologic diagnosis of PML-IRIS is challenging, particularly when the consequence of JCV reactivation and immune reconstitution is not clear,” the researchers wrote. “The pathologic features in fingolimod-associated PML in MS may include only early and weak characteristic features with immunoreaction, differing from previously reported PML by other disease-modifying treatments (DMTs).”