Medicine & Research

Management of Progressive MS: Treatment Options are Available and Vary

By Dr. Ben Thrower
The past 25 years have seen rapid advances in our ability to alter the course of multiple sclerosis. We have gone from no FDA-approved treatment options until 1993 to 16 approved options in 2018. Challenges remain, however. One of these challenges is the management of progressive forms of MS.
Before we can effectively manage a progressive form of MS, we must accurately diagnose it. There are two forms of progressive MS – primary and secondary. Primary progressive MS is felt to represent about 10 percent of the MS community. It typically starts later in life than relapsing forms of MS and, unlike relapsing forms of MS, is just as common in men as it is in women. Primary progressive MS typically presents with slow progression of walking impairment over a period of years.
Secondary progressive can be more difficult to define. Approximately 85 percent of people begin their MS journey with a relapsing form of MS. The natural history of untreated MS sees people moving towards a secondary progressive form of the disease over time. Without treatment, approximately 50 percent of relapsing forms of MS will have transitioned to a secondary progressive form over 10 years. Relapsing-remitting MS and secondary progressive MS should not be thought of as different "boxes," but as a spectrum. People with secondary progressive MS can still have relapses and new lesions on MRI.
The management of any form of MS can typically be broken down into:
• Treating and managing relapses
Managing symptoms
• Altering the disease course by lessening the likelihood of new MRI lesions, relapses, or progression of disability

Research is shedding new light and moving us closer to a fourth treatment possibility – reversal of disability.
Symptom management
In a moment, we will talk about treatment options for altering the course of progressive forms of MS, but let’s not forget symptom management. In terms of improving a person's quality of life, symptom management should not be overlooked. Regardless of whether a person is struggling with fatigue, spasticity, bowel and bladder symptoms, or mobility issues, treatment options are available. While all forms of MS benefit from a comprehensive and integrated treatment approach, this is especially true with progressive forms of MS. The management of symptoms in progressive MS does not 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 primary progressive MS. In general, ocrelizumab has a favorable safety profile. The drug is typically given intravenously every six 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 may be 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).
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 capacity to regenerate a "fresh" immune system, 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 seems to work best in the younger patient with an aggressive relapsing form of MS, with less impressive results in progressive forms of MS.
Earlier, we discussed the transition from relapsing-remitting to secondary progressive. Given that this transition is not always black and white, the use of any therapy approved for relapsing forms of MS may be discussed in secondary progressive forms. For people with MS who are already on treatment, the question sometimes arises, "How do I know if I have moved into secondary progressive?" Many people with MS still see some slow progression of disability in spite of treatment.

This presents a difficult situation. It could be that their treatment is preventing relapses and new lesions, completely stopping the progression of disability. Stopping treatment may then allow for relapses and new MRI lesions to occur. Unless a better treatment option is available in these cases, it may be safest to continue with a therapy.
Turning back the clock
Mesenchymal stem cells, clemastine, and anti-lingo are all currently being researched as options for turning back the clock and repairing damage caused by MS. Research continues to move forward towards a day when we can hopefully reverse disability.