<p>Relapses are becoming uncommon in patients with multiple sclerosis (MS), particularly because of the highly effective therapies that are now available. However, even without the presence of new magnetic resonance imaging (MRI) lesions or relapses, some patients experience ongoing symptoms and disease progression. This highlights the importance of developing strategies to prevent the accumulation of disability, regardless of its source.</p>

In MS, disease activity is clearly associated with disease worsening or relapse-associated worsening, and some patients may recover. However, with the use of highly effective therapies, we are now seeing low levels of these types of relapses. What we are noticing now, though, is that, even without new MRI lesions or relapses, patients are having ongoing symptoms and, sometimes, disease progression. This has highlighted the concept of progression independent of relapse activity (PIRA) in MS, which appears to be a separate pathologic process. Therefore, the keys to treatment in MS would be not only to reduce relapses (because relapses are clearly associated with worsening and incomplete recovery after such events) but also to try to prevent PIRA from happening. PIRA may be part of the central nervous system inflammatory response to lesions that have already occurred. Clearly, we need to aggressively treat early and prevent relapses and MRI lesions from occurring in the first place. However, therapies are needed to work on chronic active lesions and other pathologies that will reduce the risk of PIRA.

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With respect to disease-modifying therapies and PIRA, our disease-modifying therapies are reducing relapses and MRI lesions by more than 90%, but the reductions in PIRA and disability are not impacted at the same level. I do think that our treatments are working to prevent PIRA, but not to the degree at which these treatments are reducing the relapse and MRI lesion side of things. It was previously thought that PIRA occurred primarily in patients with progressive MS, but studies now reveal progression early in the disease course of MS. A paradigm shift is occurring such that there are pathologies of MS that are not entirely treated even in early disease.

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An important concept is that we want to treat MS fully but not necessarily overtreat it. So, we are always trying to match patients with the therapy that will provide disease control while maintaining a good safety/tolerability profile. This is dictated by the inflammatory burden that the patient presents with, a discussion of their beliefs and treatment goals, and then an attempt to incorporate their concerns into selecting a therapy that has a high likelihood of success without incurring excessive risk for their disease. We need to explain to the patient that we have this window of opportunity to treat MS early while it is still in the inflammatory stages (for which we have treatments that are highly effective) so that we may be able to prevent the downstream consequences of chronic lesions and the influence that they can have on disease progression and disability.

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Elements of wellness and maintaining a healthy lifestyle also factor significantly into the course of the disease. Encouraging patients to be active, to exercise, and to maintain good cardiovascular and strength fitness should all be recommended because, if a relapse were to occur, having a baseline high level of activity will help the recovery process and will prevent disability from accumulating as quickly. Engaging in a home exercise program and eating a healthy diet in moderation, with foods of nutritional value to maintain a healthy weight, are a big part of what we counsel patients with MS to do at each visit.