19 msfocusmagazine.org always mean medications. Exercise, wellness, and rehabilitation should be the foundation for symptom management, with medications used in a thoughtful and limited fashion, if possible. Treatment options Currently, there are two FDA-approved disease-modifying treatment options for progressive forms of MS. Mitoxantrone (Novantrone) is approved for secondary progressive MS, but is used infrequently. The side-effect risk of mitoxantrone may outweigh any potential benefits for most people. The drug carries a lifetime cumulative dose due to the risk of damage to cardiac muscle with resulting congestive heart failure. In addition, mitoxantrone has been associated with a significant risk of life-threatening acute myeloid leukemia even after small doses. Ocrelizumab (Ocrevus) is approved in the United States for relapsing-remitting and primaryprogressiveMS.Ingeneral,ocrelizumab has a favorable safety profile. The drug is typicallygiven intravenouslyeverysix months. It is a slow infusion with about six hours required to administer the full dose. Prior to starting Ocrevus, patients must be screened to ensure that they have antibodies to varicella (chickenpox). If the patient has no immunity to chickenpox, they should be vaccinated prior to starting ocrelizumab. Screening is also done to rule out hepatitis B. Ocrelizumab should not be administered to patients with a history of hepatitis B. Two cases of PML have been described in MS patients using Ocrevus. The first occurred in a patient switching from natalizumab (Tysabri) to Ocrevus. The second one was in an individual moving from fingolimod (Gilenya) to Ocrevus. The package insert for Ocrelizumab notes that "an increased risk of malignancy with Ocrevus may exist." In one clinical study of ocrelizumab, six women out of 781 on the drug developed breast cancer. In the Rebif comparator arm, no women developed breast cancer. The natural history of breast cancer would have suggested that 11 women in each arm would have developed the malignancy. Ocrelizumab has a similar mechanism of action to rituximab. The latter has been available for years and has been used off label to treat MS and neuromyelitis optica. No increased risk of cancer has been seen with rituximab. Looking ahead More treatment options for progressive forms of MS maybe on the horizon. Siponimod is an oral medication with a mechanism of action similar to fingolimod (Gilenya). Study results published in March 2018 showed the drug slowed progression of disability in secondary progressive MS. Hopefully, this drug will get approval in 2018. (See RX Update on page 57). Recently, there has been increased interest in autologous stem cell transplantation in MS. Study groups from the U.S., UK, and Canada have all provided updates on their treatment results. This procedure involves harvesting immature stem cells from the individual with MS. These particular stem cells have the capacitytoregeneratea"fresh"immunesystem, one without the tendency to attack myelin and axons. The person with MS is then given chemotherapy to wipe out the existing immune system. The harvested stem cells are infused back into the patient's bloodstream so that a new immune system can be generated. Research has shown that this procedure