COPENHAGEN—Risk stratification can help neurologists determine whether to prescribe one of the newer multiple sclerosis (MS) drugs for their patients, according to a lecture given at the 29th Congress of the European Committee for Treatment and Research in MS. Natalizumab, fingolimod, and alemtuzumab have potentially serious side effects, but their benefits outweigh their risks, said Per Soelberg Sørensen, MD, Head of the Danish MS Center at Copenhagen University Hospital.

“MS is a serious disease, particularly active MS,” said Dr. Sørensen. “Therefore, people need these drugs to control the disease.”

JCV Antibody Status Influences Treatment With Natalizumab
Before treating a patient with natalizumab, a neurologist should administer a blood test and an MRI, according to the European Medicines Agency. Because natalizumab entails the risk of progressive multifocal leukoencephalopathy (PML), the neurologist should determine whether the patient has antibodies to the John Cunningham virus (JCV). Patients with no JCV antibodies have almost no risk of PML, said Dr. Sørensen. Patients who have the antibodies and have used immunosuppressants are at considerable risk for PML and should not take natalizumab, he added. For patients with JCV antibodies who have not used immunosuppressants, the risk of PML is low within the first 24 months of treatment with natalizumab, but it increases during the following 12 months.

Treatment with natalizumab should be stopped if a patient develops hypersensitivity reactions or antibodies against natalizumab, according to Dr. Sørensen, who added that neurologists should monitor liver function and perform annual MRIs for all patients taking the drug. In addition, he advised neurologists to test for JCV antibodies every six months and noted that JCV antibody titer may increase for patients who begin treatment with a low titer. If the neurologist suspects that the patient is developing PML, he or she should stop natalizumab treatment, perform MRI, and perform CSF tests for JCV, said Dr. Sørensen.

Antiarrhythmics and Antineoplastics May Interfere With Fingolimod
Fingolimod, a sphingosine-1 phosphate receptor modulator, helps patients by acting on lymphocytes but may cause macular edema or restrict respiratory flow. The drug is contraindicated in patients who are taking antiarrhythmic, antineoplastic, or immunosuppressant drugs. Neurologists should be cautious when prescribing fingolimod to patients receiving drugs that lower the heart rate (eg, calcium channel blockers and beta-blockers) or medicines that inhibit CYP3A4-mediated metabolism, said Dr. Sørensen. Fingolimod initially decreases a patient’s white blood cell count, and it takes more than four weeks for the count to return to normal. Patients on fingolimod therefore should not receive attenuated live vaccines. Neurologists also should be vigilant for unknown safety signals, added Dr. Sørensen.

Blood and liver function tests are recommended before initiating treatment with fingolimod, and high-risk patients should undergo ophthalmologic exams. Neurologists should observe all patients for six hours during treatment initiation. Because of a risk of infection, clinicians should monitor patients for two months following treatment initiation, said Dr. Sørensen. During treatment, patients should report symptoms of infection and use contraception, and their blood pressure and liver function should be monitored regularly as well, he added.

Alemtuzumab Entails a Risk of Thyroid Disorder
Alemtuzumab is associated with many side effects, most of which are related to the infusion. Approximately 36% of patients develop a thyroid disorder while taking alemtuzumab, and the peak incidence occurs during the second or third year of treatment. About 1% of patients develop immune thrombocytopenia, which, like thyroid disorder, typically occurs during the second or third year of treatment. Diagnosis is important because immune thrombocytopenia responds to standard medical treatment, said Dr. Sørensen. In addition, some patients have developed neuropathy on alemtuzumab, and early detection can improve the patient’s prognosis, he added.

To maximize safety, neurologists should perform a blood test and screen for tuberculosis or HIV before initiating alemtuzumab. Patients who are anti-thyroid peroxidase positive at baseline are more likely to have thyroid-related adverse events on alemtuzumab, said Dr. Sørensen.

To prevent infusion-related reactions, neurologists can administer corticosteroids, antihistamines, and antipyretics during the first three days of treatment. Patients’ pulse and blood pressure should be monitored, and patients should receive an oral antiherpes medication for at least one month after receiving alemtuzumab, noted Dr. Sørensen. Neurologists should perform blood tests and monitor thyroid function regularly, he added. “This [monitoring] has to continue for four years after the last dose of alemtuzumab,” said Dr. Sørensen.

Monthly tests for blood count and urinalysis and thrice-monthly tests for thyroid function are recommended until four years after the last dose of alemtuzumab, although this regimen may pose logistic problems, he noted. Patients on alemtuzumab also should use contraceptives and report symptoms of infections and signs of bleeding, Dr. Sørensen concluded.

—Erik Greb
Senior Associate Editor

Risk Stratification May Mitigate Adverse Events Associated With Newer MS Drugs