This New England Journal of Medicine article provides an excellent review of the mechanism of action, clinical use and adverse effects of the new multiple sclerosis drug fingolimod (Gilenya, Novartis). Since fingolimod has been shown to be associated with a small number of cases of macular edema, ophthalmologists are being asked to prescreen and monitor patients who begin treatment with this medication.
Macular edema has been confirmed by ophthalmologic evaluation in less than one percent of patients in fingolimod clinical trials and extension studies. Most of these cases were asymptomatic and resolved within months after discontinuation of fingolimod therapy.
The article's authors recommend referral to an ophthalmologist before the initiation of fingolimod therapy, at least until the actual risk of macular edema is known. They suggest a repeat ophthalmologic evaluation three months after the initiation of treatment and every six months thereafter.
In the article, they present the case of a 37-year-old man with multiple sclerosis being evaluated for oral immunotherapy. He had reported acute monocular visual disturbance six years earlier. A diagnosis of multiple sclerosis was confirmed by means of examination of cerebrospinal fluid, which revealed an increased IgG index and oligoclonal banding, and by abnormal results on MRI.
The authors explain that they would offer oral fingolimod after reviewing the risks and benefits for this patient and performing appropriate laboratory testing, baseline ophthalmologic and dermatologic evaluations and other evaluations (including electrocardiography).
They note that although fingolimod has been approved as a first-line drug for the treatment of multiple sclerosis, they believe it should be reserved as a second-line drug until long-term safety investigations have evaluated the risks of infectious complications and secondary cancers. They say that a substantial number of patients with multiple sclerosis have a good response to first-line drugs with minimal side effects, so it seems prudent to initiate treatment with these drugs at the first evidence of a clinically isolated syndrome in a patient with abnormal MRI findings consistent with a demyelinating process.
However, considering the apparent benefits from the greater clinical efficacy of agents affecting T-cell migration (natalizumab and fingolimod) and the consequences of chronic inflammation of the central nervous system associated with multiple sclerosis, they recommend a relatively low threshold for initiating second-line therapies when permanent clinical signs of central nervous system injury are present. Since it has been shown that natalizumab therapy is associated with an increased risk of progressive multifocal leukoencephalopathy and this risk correlates with the presence of anti-JC virus antibodies, they recommend that the choice between natalizumab and fingolimod be based principally on the results of tests for these antibodies.
Before initiating fingolimod therapy, a number of other specific laboratory tests and assessments should be performed, the authors say. However, there are no established clinical guidelines for the use of fingolimod in patients with multiple sclerosis.
The authors believe that fingolimod therapy should currently be considered only for patients who have had recent inflammatory disease activity (one or more relapses or new white-matter lesions on MRI within the past year) and those who do not benefit from or cannot tolerate alternative disease-modifying therapies.