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Here is My Question:
My neurologist agrees that I have entered into SPMS, and after a major relapse about a year ago, I ceased Rebif, and started Gilenya. Since then symptoms have subsided, but not entirely disappeared. However, I now have symptoms insidiously creeping up on me, and am slowly losing more function. Since Gilenya, my WBC count is lower, but well within the range that my neurologist wants to see. I have had no infections since starting Gilenya.
My neurologist now suggests a course of chemotherapy (mitoxantrone - 3 doses each one month apart), and I'd like to know more about the pro's, con's and side effects of this treatment.
Mitoxantrone is used infrequently since the updated report of the therapeutics and technology assessment committee of the AAN in 2010. This report and the various studies that predated this report, heightened our concern for Cardiac dysfunction (12 %), Congestive heart failure (0.4 %) and treatment related leukemia (0.8 %) in patients who have been treated with mitoxantrone. The FDA now recognizes that these concerns may emerge even early in treatment and recommend an echocardiagram after each treatment.
If your rate of decline in function is rapid and if there is still evidence of active disease on MRI (esp. if you are under 50) then several other options exist including Tysabri, rituximab and monthly cyclophosphamide. My preferred treatment for patients under 50 with transitional MS (transitioning from relapsing to progressive with continued activity) is rituximab, if your are able to obtain insurance approval. I will sometimes use Rituximab as induction therapy in this circumstance, if the rate of decline is rapid, followed by Tysabri, if the individual is JC virus antibody negative. If not a rapid rate of decline, I will go directly to Tysabri with or without monthly IV steroids for 1 to 3 courses. If an individual is JCV antibody positive (high index) and they have active disease, I will use cyclophosphamide if unable to get rituximab approved.
Of course, there is no class I evidence to support these approaches at present. Tysabri is approved for relapsing MS but trials in late relapsing or secondary progressive MS are still underway; rituximab and cyclophosphamide are off label agents in MS but used frequently around the world. The evidence suggests that PML is relatively rare in rituximab treated patients (as compared to Tysabri) and we do not have the high risk of cardiac toxicity or treatment related leukemia with cyclophosphamide treatment.
Talk it over with your MS specialist and see what he or she thinks
Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Professor of Clinical Neurosciences
University of California San Diego
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