Conference Coverage

Risk Stratification Can Guide the Choice of MS Treatment



BOSTON—The emergence of many new disease-modifying therapies in the past 10 years has made it more challenging to choose a drug for a patient with multiple sclerosis (MS), according to an overview provided at the 2014 Joint ACTRIMS–ECTRIMS Meeting. In the United States, 12 FDA-approved therapies, including oral medications, are available for the long-term treatment of MS. These medications’ efficacy, tolerability, and safety differ widely, and patient-specific risk factors can be an important guide for choosing the appropriate treatment, said Robert Fox, MD, Vice Chair for Research at the Cleveland Clinic.

Head-to-head comparisons indicate great similarity among injectable MS therapies, which generally reduce annualized relapse rate by about 30%. The choice of an injectable therapy should be influenced by the expected side effect profile, the patient’s risk factors, patient preference about the frequency of administration, and the clinician’s comfort with the drug, said Dr. Fox. Risk stratification and mitigation should continue over time because risk factors can change, thus altering an individual’s risk for a complication.

Robert Fox, MD

Interferon and Glatiramer Acetate Interferon and glatiramer acetate are considered relatively safe medications, but they still require risk evaluation and mitigation, Dr. Fox said. Nonsteroidal anti-inflammatory agents and hydration can mitigate interferon’s flu-like side effects, and monitoring can reduce the drug’s associated risks of increased liver enzymes and leukopenia. Screening patients for headache, pain syndromes, and depression is also warranted before and during interferon treatment.

Glatiramer acetate entails risks of erythema, lipoatrophy, induration, and immediate post injection systemic reaction. Education and proper injection technique can mitigate the risk of skin reactions, and “education is of high importance for the post injection systemic reaction and can help avoid needless trips to the emergency room,” said Dr. Fox.

Researchers have identified three main factors that can stratify the risk for progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab: John Cunningham virus (JCV) infection, prior immunosuppressant use, and duration of natalizumab treatment. Patient counseling and decision making depend greatly on which risk factors the patient has, said Dr. Fox.

Natalizumab is considered relatively safe for patients who are JCV negative, but seroconversion may occur over time. Neurologists can consider other therapies for individuals who are JCV positive, but if good alternatives are not available, the clinician may consider limiting natalizumab treatment to one to two years. Natalizumab should be avoided for patients with prior immunosuppressant use if reasonable alternatives are available. Neurologists should be vigilant for symptoms suggestive of PML and could consider performing an MRI at least every six months in JCV seropositive patients.

Antinatalizumab antibodies, which can develop particularly with prior natalizumab use, and history of anaphylaxis increase the risk of allergic reactions to natalizumab, Dr. Fox noted. Liver enzyme screening at baseline and close monitoring for patients with a history of liver disease can mitigate the risk of elevated liver enzymes.

Fingolimod, particularly the first dose of the drug, entails a risk of cardiac events, and concomitant medications can increase this risk. Obtaining a cardiac history is advisable before patients start fingolimod. In addition, neurologists should perform baseline EKG, first-dose observation, and a post first-dose EKG for the patient. A standard observation lasts for six hours and includes frequent monitoring of vital signs. A 24-hour observation is indicated in patients with certain risk factors.

Fingolimod also carries a risk of macular edema that may be higher in older people or those with a history of diabetes or uveitis. Neurologists therefore should perform optical coherence tomography at baseline and at three months, said Dr. Fox. Patients with visual symptoms should be evaluated promptly for possible macular edema.

Because the drug is associated with a risk of herpes virus infections, patients should be screened for varicella zoster serology, even if they have a history of chicken pox. Seronegative patients require vaccination before starting fingolimod. Other risks include lymphopenia and leukopenia, and neurologists can monitor for these outcomes through intermittent complete blood count testing. Repeated liver function panels may mitigate the risk of increased liver enzymes, and headaches and back pain can be treated symptomatically.

Teratogenesis may be the biggest concern for patients treated with teriflunomide, which is labeled as pregnancy category X. Alternative therapies could be considered for people of childbearing potential, said Dr. Fox. Patients who receive teriflunomide should use contraception. Certain treatments can accelerate washout if a patient wants to become pregnant or inadvertently becomes pregnant while taking teriflunomide.

Teriflunomide may increase liver enzymes, therefore monitoring is appropriate. The drug is relatively contraindicated for patients with previous liver injury secondary to medications, liver disease, or tuberculosis, added Dr. Fox.

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