Multiple Sclerosis (MS) the prototypical inflammatory demyelinating disease of the central nervous system is defined as intermittent neurologic dysfunction at least twice separated in time and space. As such treatment of MS is mainly anti-inflammatory in nature, but the developments in the last decade have changed the landscape of MS treatment.
Multiple Sclerosis (MS) most common disabling disease of young adults is mainly autoimmune in nature thus treatment of MS is mainly anti-inflammatory.
Treatment of MS evolved over the last 20 years and includes management of acute attacks with glucocorticoids, prevention of acute attacks with DMTs and management of disability symptoms.
Future of MS treatment is going to involve treatment options to possibly reverse disability and cure the disease by “reeducating” the immune system, or at the very least safer, more effective and highly specific “newer” generation DMTs.
Goals of Treatment
MS is a chronic disease with no known cure. Thus, the current goal of medical management is the prevention of disability as well as improvement of quality of life and possibly mitigation of current disability. Treatment is also categorized as either control of acute attacks, disease modifying therapy (DMT) and symptom management.
Management of Acute Exacerbations
The initial goal of management of an acute attack is to ensure that possible confounders such as infections or other illnesses are ruled out as diseases such as sinusitis or urinary tract infections can cause MS exacerbations. There are several treatment options depending on the severity of the presentation, however, treatment of acute attacks has not been shown to have any effect on long-term disability. Treatment options for Acute Exacerbations include:
- Intravenous Methylprednisolone (IV Glucocorticoids): IV corticosteroids in brief courses and high doses are the mainstay of treatment of acute exacerbations. High dose IV methylprednisolone shortens the duration of exacerbation, slows progression of deficits as well as improves MRI measures of disease.
- Oral prednisone (Oral Glucocorticoids): Bioavailability of oral prednisone is similar to intravenous therapy and some patients prefer oral therapy to intravenous as they can skip possible hospital admission as well as intravenous lines. Most studies also demonstrate similar efficacy between IV and Oral formulations.
- ACTH: Some patients present a challenge with IV access or do not tolerate high-dose glucocorticoids, necessitating treatment with adrenocorticotropic hormone (ACTH) to get their adrenal glands to secrete glucocorticoids. ACTH is typically injected intramuscularly and is thought to have a similar benefit as methylprednisolone.
- If the attack is refractory, further treatment can be either plasma exchange, where the plasma (part of blood that carries proteins, antibodies and similar substances) of the patient is filtered and exchanged; or immunoadsorption to remove autoantibodies from the plasma.
Disease-modifying Therapy (DMT)
Disease-modifying therapy is the cornerstone of MS management. DMTs decrease the frequency of acute exacerbations and thus delay any possible disability. There are several different DMT options available that are mainly grouped in three different categories:
- Monoclonal Antibodies: Monoclonal antibodies include natalizumab, rituximab, alemtuzumab amongst others, and are used in patients with active disease that are risk tolerant and want effective treatment as there can be serious side effects. For example, natalizumab prevents the leukocytes (white blood cells) from passing through the blood-brain barrier thus reducing new brain lesions and exacerbations, however, can increase risk of progressive multifocal leukoencephalopathy (PML).
- Oral Therapies: Oral therapies are mainly fumarates such as dimethyl fumarate and sphingosine 1-phosphate (S1P) receptor modulators such as fingolimod. Oral therapies are preferred in patients that would prefer to self-administer and are averse to injections. Although oral therapies are relatively safer, they may still be associated with severe side effects. For example, fingolimod can cause persistent bradycardia or macular edema. Fumarates on the other hand are known to cause full-body flushing, gastrointestinal issues as well as headache.
- Other injectable therapies: Other injectable therapies include human interferon beta-1b and 1a as well as glatiramer acetate. These medications were the initially approved DMTs and are thus called “platform” therapies. They can be preferred in patients that value safety more so than effectiveness and convenience. Both interferon beta and glatiramer are thought to interfere with formation of new demyelinating plaques. Interferon beta is metabolized hepatically thus warrants periodic lab work, along with flu-like side effects. Glatiramer, while Is safer from a side effect perspective can take up to 9 months to show clinical effectiveness.
Symptom management is to help manage symptoms such as fatigue, gait impairment, spasticity as well as tremor and urinary dysfunction. Approach is individualized but typically consists of both non pharmacological and pharmacological management:
- Fatigue is initially managed by ensuring any associated conditions such as hypothyroidism or anemia are ruled out and/or appropriately managed. Exercise programs are also usually utilized as well as possible medications such as amantadine or modafinil.
- Gait is initially managed non-pharmacologically. Resistance training has been shown to help improve balance, as well as virtual reality training. For unresponsive cases, dalfampridine can be utilized, which has been shown to improve gait endurance and increase gait speed.
- Spasticity is usually extremely unpleasant and painful in patients with MS owing to the most common localization of legs. Baclofen is commonly used in this context along with localized botulinum toxin injections.
- Urinary dysfunction on the other has no guideline or consensus-based management. It is handled on a case-by-case basis and with various approaches such as mind-body therapies, oxybutynin or botulinum toxin injections.
Future of MS Treatment
Although DMTs have turned the chapter in MS management, they’re still not curative. Ongoing research in stem cells is trying to see if stem cell transplantation can help reverse or even cure the disease by helping reteach the immune system and stop it from attacking the myelin sheath of the central nervous system.
Researchers are also looking at various pharmaceuticals to help regenerate the damaged myelin sheath in hopes of reversing disability.
There’re also newer DMTs in various stages of study. For example, one ongoing study is looking at Vidofludimus calcium (IMU-838), as a newer DMT. Proposed advantages include increased specificity thus better safety and less side effects.
Finally, one of the emerging groups of DMTs is called Bruton’s tyrosine kinase (BTK) inhibitors. They’re being tested in late-stage trials for different types of MS and the purported advantages include crossing the blood-brain barrier as well as more selectively targeting immune cells to minimize side effects.