1. 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

2. 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

3. 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

4. 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

5. 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

6. 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