Fingolimod Therapy for Multiple Sclerosis Anne H. Cross, MD Professor and Director John L. Trotter Multiple Sclerosis Center Department of Neurology Washington University School of Medicine St. Louis, Missouri Mary A. Willis, MD Neurological Institute The Mellen Center for Multiple Sclerosis Treatment and Research Cleveland Clinic Cleveland, Ohio

Fingolimod–Time to Benefit MRI is surrogate measure of efficacy In FREEDOMS and FREEDOMS II, MRI was done at baseline and 6, 12, and 24 months Based on analysis of these data, MRI evidence of effect on inflammation and neurodegenerative pathology can be seen early Gadolinium-enhanced lesions were reduced versus placebo at all time points Reduction in brain volume was observed at 6 months

Key Monitoring for Fingolimod Adverse Effects Pregnancy test for women with reproductive potential prior to starting fingolimod Electrocardiogram prior to starting fingolimod Refer to cardiologist if abnormal Complete blood count and liver function tests at first follow-up after starting fingolimod (eg, at 3 months) Ophthalmologic exam 3 to 4 months after starting fingolimod

Wash-out Recommendations No established guidelines, only recommendations based on knowledge of a drug’s kinetics or effect on blood parameter After natalizumab For most patients, wait 3 months before starting fingolimod After interferon beta No wash-out needed After glatiramer acetate After teriflunomide or dimethyl fumarate Not yet known For dimethyl fumarate, consider following white blood cell count to identify time to start fingolimod

Do These Drugs Have Interaction Issues with Fingolimod? Dextromethorphan hydrobromide plus quinidine sulfate used for pseudobulbar affect Although quinidine as a class I antiarrhythmic is contraindicated, this combination product has 10-fold less quinidine At least 1 case series has shown no adverse effects Dalfampridine No interaction between dalfampridine and fingolimod Dalfampridine has low risk of induction of QT prolongation and associated cardiac arrhythmias in healthy individuals

Role of Fingolimod in MS Treatment Algorithm Approved as first-line therapy for relapsing forms of MS Also appropriate as alternative therapy in patients with: Breakthrough disease Intolerable side effects Poor adherence