A New Era of Multiple Sclerosis Treatment

Prior to 1993, no approved treatments were available for multiple sclerosis (MS). People who developed MS prior to the first treatments, unfortunately, had damage to their brain and spinal cords which often led to progressive disability. MS relapses are bouts of neurological symptoms such as numbness, weakness, imbalance and visual loss that can last days to months.

The first generation of self-injected medications reduced relapses by about one-third and as much as 80% of new brain disease seen on MRI (magnetic resonance imaging) scans. These medications fight the immune attack on the brain and spinal cord without compromising the body’s ability to fight infections.  Tysabri (natalizumab), an infusion therapy  given in the vein monthly, dropped relapses by 68% compared to placebo in clinical trial and has been available for treatment for over a decade.

Over the past 7 years, an array of new oral and antibody treatments for MS have become available that have unique effects on the immune system to block MS.  Oral therapies are Aubagio, Gilenya and Tecfidera and new monoclonal antibody therapies are Lemtrada, Ocrevus, and Zinbryta.  Some oral therapies have been shown to reduce relapses by more than half compared to placebo.  Gilenya and Zinbryta demonstrated a superior reduction in relapses compared to Avonex.  The advantages of good disease control must be balanced against serious risks of these drugs even if some risks are uncommon or rare.

Lemtrada (alemtuzumab) is a highly effective antibody therapy that in clinical trials has  reduced relapses by half compared to Rebif. On Lemtrada, 43% of patients actually had less disability confirmed at end of 6 years compared to the onset of the study.  Another antibody treatment, Ocrevus (ocrelizumab), also showed in clinical trials to reduced relapses almost in half and reduced contrast MRI activity by 95% compared to Rebif. Lemtrada transiently depletes T and B cells and Ocrevus consistently depletes B cells with potential serious risks including serious infusion reactions and serious infections.

Treatment Stategies

One common approach to treating multiple sclerosis is starting with a self-injected medication with two decades of long-term safety information. These medications including Copaxone (glatiramer acetate) and interferons (including Avonex, Betaseron, Extavia and Rebif )have been effective for many patients without immune compromise. If new relapses, worsening disability or unchecked MRI activity occur, the first medication could be switched to another agent.   The strategy is often referred to as “escalation” of treatment. This approach may be the safest option, but waiting too long to switch therapies may result in irreversible disability.

Another strategy is to seize the moment.   People living with MS without new relapses and without new MRI activity have the best chance of preventing disability progression. One goal of MS treatment is achieving NEDA (No Evidence of Disease Activity) which means a patient is free of relapses, disability progression and MRI activity. Choosing a high-powered medication first to minimize risk of worsening disability to maximize quality of life is another treatment approach. Early in MS there can be changes such as nerve injury that may lead to irreversible disability. This earlier treatment approach  tackles the disease aggressively from the start.  Accepting potential long-term risks of these immune therapies with a lifelong disease is one concern. In addition, the use of some of these immune treatments might restrict the next treatment option. Not all therapies are indicated for first-line therapy in the United States.

Likely the best approach is a combination. This strategy involves stratifying the risk of disease, then matching with an appropriate medication. Some risk factors that increase risk for disability include being male, MS onset after age 40, incomplete recovery from first attack, frequent relapses the first 2 years of disease, spinal cord disease and higher amount of MS changes on initial MRI. Patients with lower risk of disability progression may choose a more conservative medication option. In contrast, someone at higher risk for disability may be willing to accept more risk for more effective treatment. It is critical for individuals living with MS to share their willingness to accept or not accept certain risks to control their disease. Neurologists also vary in their willingness to use higher risk medications which often influences the decision process. Each person living with MS should meet with their neurologist to clarify their individual risk of disability based on their disease.

Research advancements have led to a growing array of new MS therapies. To determine the best individualized treatment plan, being informed and open with healthcare providers is essential.