Treatment Approaches for Multiple Sclerosis

Multiple sclerosis (MS) is the most common disabling disease of the central nervous system in young adults. The condition impacts the brain and spinal cord, and most commonly affects a person’s vision, balance, mobility, and various other bodily functions. As such, doctors use a combination of prescribed medications, including anti-inflammatories and steroids, to treat symptoms. However, because scientists have yet to find a cure, these drugs can only help to reduce or slow the effects of symptoms.

Managing the acute MS attacks

Multiple sclerosis is a disease characterized by acute attacks with differing recuperation periods depending on the subtype of MS. As such, the main goal of treating an acute relapse is to treat it as quickly as possible to limit its effect on function. As such, the standard approach calls for administering high-dose glucocorticoids — steroid hormones — at the first signs of acute worsening after ruling out other factors such as infections.

Clinically Isolated Syndrome & Radiologically Isolated Syndrome

Clinically isolated syndrome (CIS) refers to the initial symptomatic episode lasting more than 24 hours but whose symptoms can’t be attributed to other causes, such as fever, before an MS diagnosis. There is sufficient evidence to show that treating CIS with disease-modifying therapy (DMT) is beneficial. DMT options such as interferon beta or glatiramer are warranted for patients that have additional clinically silent lesions detected by MRI, and such treatment reduces the risk of progression to a full MS diagnosis. While the data doesn’t address the most appropriate length of treatment, it would be reasonable to discuss discontinuation of DMT in patients with CIS that remain stable without new lesions for several years.

Radiologically isolated syndrome (RIS), on the other hand, defines incidental brain and spinal cord MRI findings that suggest MS without any applicable symptoms. While patients with RIS are also at risk of developing CIS and MS, no clear data warrants the use of DMTs in these patients.

Managing Relapsing-Remitting MS (RRMS)

Relapsing-remitting MS (RRMS) is the most common type of MS at the onset. The patient suffers relapses in which their condition worsens but then goes into remission. During these recovery periods, the patient’s symptoms don’t deteriorate; however, they are typically worse than they were in the previous relapse. DMT is used to treat patients diagnosed with RRMS.

Furthermore, the evidence demonstrates that the earlier the treatment, the better the long-term outcomes. The most important approach to DMT in this context is shared-decision making. This strategy incorporates the patient’s opinions and values into which treatment strategies to follow. Several types of DMTs have differing side effects, effectiveness, administration, and burden profiles.

For patients with highly active disease or those that are risk-tolerant and want an effective, more aggressive approach, therapy using IV antibodies such as natalizumab is appropriate. On the other hand, for patients with less active disease and who value the convenience of self-administration of medications, less effective oral options such as fingolimod or dimethyl fumarate are appropriate. Finally, for patients that want the safest option with the lowest effectiveness, beta interferons or glatiramer are appropriate.

Subsequent adjustments in DMT are based on patient response, disease activity based on relapses, and the development of new lesions demonstrated by MRIs. Most evidence suggests that a more aggressive DMT option is warranted if a patient develops new lesions on an MRI scan after having utilized a DMT for longer than six months.

DMT is utilized indefinitely in patients with RRMS unless side effects or safety concerns become an issue.

Management of secondary progressive MS

Secondary progressive MS (SPMS) begins as RRMS, which ultimately progresses to steady deterioration. Thus, this advancement warrants more intensive therapy, with possibly more “effective” DMTs. Although all DMTs would be considered appropriate in this context, only Siponimod has been shown to be effective in reducing the risk of disability progression in a randomized trial.

It’s reasonable for patients who don’t respond to a particular DMT to switch to another. Unfortunately, there isn’t enough data to determine the most appropriate time to make such a switch. A single relapse after a long period of stability may not be sufficient to warrant a switch.

Of note, non-ambulatory patients with SPMS that have been stable for a period longer than two years may be suitable candidates for discontinuation of DMTs.

How to best treat primary progressive MS

Primary progressive MS (PPMS) is defined as progressive MS from the onset and, thus, has deceitful progression with gradually worsening gait difficulty. For young patients or those with active disease, ocrelizumab —an IV-administered medication to help reduce inflammation and nerve damage — is the treatment of choice. For older patients or those with inactive disease, ocrelizumab can also be considered.

Unfortunately, there is insufficient data to determine at what point it should be recognized that ocrelizumab treatments are ineffective. Thus, monitoring expectations annually and observing ocrelizumab’s safety is recommended.

Other DMTs such as interferons, glatiramer, or rituximab have not shown to be beneficial for patients with RRMS. Most other medications, such as glucocorticoids, have no data supporting their use and are used empirically. Consequently, in patients not responding to ocrelizumab, treatment is best handled individually and on a case-by-case basis.

Key takeaways

Multiple sclerosis (MS), the most common disabling disease of young adults, is mainly autoimmune in nature, and treatment of MS is hallmarked by disease-modifying therapy (DMT).

For patients with Clinically Isolated Syndrome, DMTs have been shown to reduce the risk of progression to MS. However, for those with Radiologically Isolated Syndrome, evidence is lacking to support treatment with DMTs.

For patients with RRMS, the treatment of choice is DMTs in perpetuity, guided by patient preferences of efficacy vs. safety.

For patients with SPMS, the treatment of choice is also DMTs, though more “efficacious” ones.

For patients with PPMS, the only treatment that has been shown to be effective is ocrelizumab.

Resources:

Comi G. Shifting the paradigm toward earlier treatment of multiple sclerosis with interferon beta. Clin Ther. 2009 Jun;31(6):1142-57.

Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: disease-modifying therapies for adults with multiple sclerosis: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology. 2018;90(17):777-788.

Bourdette D, Simon J. The radiologically isolated syndrome: is it very early multiple sclerosis? Neurology. 2009;72(9):780-781.

Lizak N, Lugaresi A, Alroughani R, et al. Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(3):196-203.

Colligan E, Metzler A, Tiryaki E. Shared decision-making in multiple sclerosis. Mult Scler. 2017;23(2):185-190.

Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018;24(2):96-120.

Wise J. Multiple sclerosis: NICE recommends treatment for secondary progressive MS. BMJ. 2020;371:m3990.

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