multiple%20sclerosis
MULTIPLE SCLEROSIS
Multiple sclerosis is an acquired chronic immune-mediated inflammatory disease of the brain and the spinal cord characterized by presence of multiple discrete areas of myelin loss within the CNS and subsequent axonal degeneration.
Affects more women than man; however, men are more likely to have a malignant clinical course.
A multiple sclerosis attack is usually characterized by any neurological disturbance with minimum 24 hours duration, in the absence of fever or infection.

Pharmacotherapy

Disease-Modifying Therapy

  • Goals: To reduce the rate of disease/disability progression, decrease the number of relapses, and help reduce development of new lesions
  • Risks versus benefits need to be reviewed with patient before starting therapy
  • Patients with relapsing-remitting multiple sclerosis that had 2 or more clinical relapses for the past 2 years can be considered as having active disease
  • Have been shown in multiple class I and class II clinical trials to significantly delay second clinical relapse or new brain magnetic resonance imaging-detected lesions in those with a first demyelinating event and considered at high risk for multiple sclerosis
  • Some live vaccines may be contraindicated in patients with multiple sclerosis that is being treated with disease-modifying therapies

Alemtuzumab

  • A monoclonal antibody that binds to CD52 antigen causing cell lysis
  • Recommended as a treatment option for adult patients with active relapsing-remitting multiple sclerosis
  • Studies showed a decrease in the relapse rate and risk of sustained accumulation of disability in patients
  • Studies have shown that it is more effective than Interferon beta-1a 44 mcg subcutaneously 3 times/week in decreasing risk of disability progression over 2 years in patients with relapsing-remitting multiple sclerosis
  • Treatment option for patients who have responded inadequately to ≥2 disease-modifying treatment for relapsing-remitting multiple sclerosis

Cladribine

  • An antineoplastic agent
  • Can be a treatment option for patients with active secondary-progressive multiple sclerosis
  • Recommended treatment option for patients with relapsing-remitting multiple sclerosis that has inadequate response to other disease-modifying treatment
  • Studies showed that it is more effective than placebo in reducing rate of relapse and risk of relapse over 2 years in patients with relapsing-remitting multiple sclerosis
  • Efficacy in decreasing risk of disability progression over 2 years was seen in a placebo-controlled clinical trial
  • Found to significantly reduce gadolinium-enhanced lesions, active T2 lesions and combined unique lesions compared with placebo in patients with relapsing-remitting multiple sclerosis
  • It may be effective in decreasing risk of converting to multiple sclerosis in patients with clinically isolated syndromes (CIS) over 3 years based on a placebo-controlled clinical trial

Dimethyl fumarate

  • A metabolite of fumaric acid that have an anti-inflammatory and anti-oxidant property that reduces oxidative cell stress
  • May be considered in patients with active relapsing-remitting multiple sclerosis whose disease is not highly active or rapidly evolving severe relapsing-remitting multiple sclerosis
  • Placebo-controlled studies showed it is effective in reducing the number of new or enlarging T2 lesions in patients with relapsing-remitting multiple sclerosis at 2 years
  • Efficacy in reducing risk of disability worsening over 2 years in patients with relapsing-remitting multiple sclerosis has been shown in 2 placebo-controlled clinical trials

Fingolimod

  • Has been shown to reduce the relapse rate in patients with relapsing-remitting multiple sclerosis based on 2 large controlled trials
  • Studies showed that it is more effective compared with placebo in decreasing the risk of new or enlarging T2 lesions at 2 years in patients with relapsing-remitting multiple sclerosis
  • Efficacy in decreasing risk of disability progression over 2 years in patients with relapsing-remitting multiple sclerosis was seen in 2 placebo-controlled clinical trials
  • May be used as an alternative in patients with active relapsing-remitting multiple sclerosis who are intolerant of interferons and Glatiramer

Glatiramer acetate

  • Alternative to Interferon in patients with active relapsing-remitting multiple sclerosis
  • Has been shown to reduce the clinical relapse rate (either clinically or by magnetic resonance imaging) in patients with relapsing-remitting multiple sclerosis
  • Relapsing-remitting multiple sclerosis patients may also have a slowing of sustained disability progress
  • A study showed that it is more effective compared with placebo in reducing the number of new or enlarging T2 lesions at 2 years in patients with relapsing-remitting multiple sclerosis 

Interferon beta-1a (intramuscular and subcutaneous) and 1b (subcutaneous)

  • Used to reduce frequency and severity of acute relapses in relapsing forms of multiple sclerosis
  • May consider use in any patient at risk for developing clinically definite multiple sclerosis (CDMS)
  • There may be certain populations of patients who are better candidates for therapy than others but it is yet to be determined how to distinguish these patients
  • Has been shown to reduce the attack rate (determined either clinically or by magnetic resonance imaging) in patients with multiple sclerosis or in patients who experienced an isolated syndrome and are at risk of developing clinically definite multiple sclerosis
  • Can be a treatment option for patient with active secondary-progressive multiple sclerosis
    • Has been shown to reduce disability progression at 3 and 6 months in patients with secondary-progressive multiple sclerosis based on 4 placebo-controlled clinical trials
    • Efficacy in reducing risk of relapse over 2 years in patients with secondary-progressive multiple sclerosis was demonstrated in a placebo-controlled clinical trial
  • Reduce disease severity (determined by magnetic resonance imaging)
  • May slow progress of disability
  • Neutralizing antibodies (NAb) may develop and interfere with long-term efficacy of treatment

Mitoxantrone

  • An antineoplastic agent
  • Used in patients with worsening relapsing-remitting multiple sclerosis and secondary-progressive multiple sclerosis to reduce frequency of clinical relapse and reduce neurological disability
    • May be more effective in reducing risk of relapse and disability progression over 2 years in patients with worsening relapsing-remitting multiple sclerosis based on a placebo-controlled study
    • Has been shown to reduce risk of disability worsening in patients with secondary-progressive multiple sclerosis based on a placebo-controlled trial
  • Should be reserved for patients with rapidly advancing disease who have failed other therapies
  • Probably reduces attack rate in relapsing forms of multiple sclerosis
  • A study showed that it is more effective than placebo in reducing the number of new lesions on T2 at 2 years in patients with relapsing-remitting multiple sclerosis
  • Efficacy in reducing risk of disability progression over 2 years in patients with relapsing-remitting multiple sclerosis was seen in a placebo-controlled trial
  • Toxic effects (eg cumulative dose cardiotoxicity) may not outweigh benefit

Natalizumab

  • Murine monoclonal antibody used as monotherapy to prevent relapses and delay progression of disability in relapsing-remitting multiple sclerosis
  • Efficacy in decreasing the risk of at least 1 new or enlarging T2 lesion at 1 year and in reducing T2 lesion load at 2 years in patients with relapsing-remitting multiple sclerosis was shown in a placebo-controlled clinical trial
  • Found to be more effective than placebo in reducing risk of disability progression at 2 years in patients with relapsing-remitting multiple sclerosis
  • Due to increased risk of progressive multifocal leukoencephalopathy (PML) in the use of Natalizumab, it is generally recommended for patients who had inadequate response to, or inability to tolerate alternative multiple sclerosis therapy
  • Recommended treatment option for patients with rapidly evolving severe relapsing-remitting multiple sclerosis

Ocrelizumab

  • An anti-CD20 monoclonal antibody approved for treatment of relapsing or primary-progressive forms of multiple sclerosis
  • First B-cell targeted therapy for adult patients with multiple sclerosis and first drug to gain US Food and Drug Administration (FDA) approval for primary progressive multiple sclerosis
  • Efficacy of Ocrelizumab for treatment of primary-progressive multiple sclerosis was seen in a placebo-controlled clinical trial that showed risk reduction in the portion of patients with 12-week confirmed disability progression
  • In 2 studies it was found to be more effective than Interferon beta-1a 44 mcg in reducing risk of disability progression confirmed at 3 and 6 months over 2 years in patients with relapsing-remitting multiple sclerosis
  • Efficacy of Ocrelizumab for treatment of relapsing forms of multiple sclerosis was seen in 2 randomized double-blind active comparator trials that showed reduced annualized relapse rates and reduced worsening of disability 
  • Recommended treatment option for patients with active relapsing-remitting multiple sclerosis where Alemtuzumab is contraindicated or not suitable
  • Can be a treatment option for patients with active secondary-progressive multiple sclerosis

Teriflunomide

  • Treatment option for active relapsing-remitting multiple sclerosis patients whose disease is not highly active or rapidly evolving
  • Studies show that administration of Teriflunomide significantly reduces relapse rate in patients with multiple sclerosis
  • Efficacy in decreasing disability progression at 2 years in patients with relapsing-remitting multiple sclerosis was seen in 2 placebo-controlled clinical trials
  • May be effective in decreasing risk of converting to multiple sclerosis in patients with clinically isolated syndromes (CIS) over 2 years as shown in a placebo-controlled clinical trial

Alternative Therapy
Azathioprine

  • An imidazolyl derivative of Mercaptopurine which inhibits RNA and DNA synthesis
  • May be a treatment option for patients with relapsing-remitting multiple sclerosis who do not have access to approved disease-modifying treatment
  • Studies have shown it is more effective compared with beta Interferons in decreasing relapse rate

Relapse Treatment

  • Goals: To reduce duration and severity of acute attacks, and reduce residual disability

Corticosteroids

  • When used short-term, has been shown to speed functional recovery in patients with acute attacks of multiple sclerosis
    • Short-term use during attacks has not been shown to give any long-term functional benefit
  • One study has shown that regular pulse glucocorticoids may be of long-term advantage to patients with relapsing-remitting multiple sclerosis, but more studies are needed
  • Methylprednisolone is used to treat acute attacks and relapses of multiple sclerosis
    • Inhibits inflammatory cascades and the activation and invasion of T cells into the central nervous system
  • Intravenous corticosteroids is preferred over oral corticosteroids because of increased risk of recurrent optic neuritis in oral steroids
  • Corticotropin available as intramuscular or subcutaneous agent is an alternative for patients who cannot tolerate high-dose corticosteroids or who have poor venous access or prefer self-administration

Muscle Relaxants

  • Along with physiotherapy, muscle relaxants are one of the mainstays of management of spasticity
  • Eg Baclofen, Dantrolene, Eperisone, Tizanidine, Tolperisone
  • These drugs act via different mechanisms:
    • Baclofen is thought to act at the spinal cord level but may have supraspinal sites of action and is a powerful neuronal depressant and may exert its inhibitory effects by acting as agonist at gamma aminobutyric acid (GABA) receptors
    • Dantrolene acts directly on the muscles, possibly by interfering with the release of calcium from muscular sarcoplasmic reticulum needed for contraction
    • Eperisone is a centrally acting muscle relaxant which may also have a vasodilator action
    • Tizanidine is a centrally acting relaxant and alpha-adrenergic agonist thought to act at spinal and supraspinal levels by inhibiting the presynaptic activity of excitatory interneurons
      • It may produce additive effects to Baclofen, allowing a reduction in the dosage of both drugs
    • Tolperisone is also a centrally acting muscle relaxant

Non-Pharmacological Therapy

Gingko Biloba

  • Various evidence have shown that gingko biloba intake helps relieve fatigue but is ineffective for improvement of cognitive function

Magnetic Therapy

  • Found effective in reducing fatigue in relapsing-remitting multiple sclerosis
  • Further studies are needed to prove efficacy of magnetic therapy in reducing multiple sclerosis-related disabilities

Neurologic Deficit Rehabilitation

  • Multidisciplinary assessment by experts
  • Programs which are goal-oriented; needs of the individual will change over time so goals will need to be adjusted
  • Comprehensive management will involve:
    • Input from a number of modalities
    • Patient education and provision of information
    • Therapy from many different disciplines, including drug therapy

Plasmapheresis

  • Should be considered only in rare cases of relapse that have poor response to treatment with high-dose corticosteroids or do not respond to intravenous corticosteroids
  • Not recommended for chronic primary-progressive multiple sclerosis or secondary-progressive multiple sclerosis

Reflexology

  • May provide temporary reduction of multiple sclerosis-related paresthesia

Symptomatic Therapy

  • Patients tend to suffer from a range of symptoms
  • Symptoms change over time; constant re-evaluation is needed
  • Management needs to be individualized
  • Consider the impact of treatment of one particular symptom on the other symptoms

Therapy Goals

  • Improve function
  • Ease discomfort
  • Prevent secondary complications and disability
Editor's Recommendations
Most Read Articles
Roshini Claire Anthony, 30 Nov 2019

A target low-density lipoprotein cholesterol (LDL-C) level of <70 mg/dL appeared to reduce the risk of major cardiovascular (CV) events* following an atherosclerotic ischaemic stroke, according to results of the Treat Stroke to Target trial.

13 Aug 2018
Associate Professor Reshma A Merchant, Head & Senior Consultant of the Division of Geriatric Medicine at the National University Hospital, Singapore, speaks with Audrey Abella to discuss the challenges associated with dementia, its impact on the ageing population, and how this condition can be best managed in primary care.