Journal Club

Promising New Treatment Regimens For Multiple Sclerosis


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Click on the link at left to go to your desired page:  Introduction  Page 2  Page 3  Study 1  Study 2  Conclusion  Post-Test


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In 2002 guidelines were published for treatments aimed at improving the course of Multiple Sclerosis.1

The Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines set clear interpretation guidelines and cautions for studies that evaluate treatments.2  They suggested that because most studies have duration of two years or less short-term endpoints should be used.  In addition, a p-value of less than 0.01 is more appropriate to demonstrate a beneficial effect of a treatment while a p value between 0.01 and 0.05 could be considered marginal.  Studies should also be powered to detect any parameters such as disease progression, and even though an effect may be statistically insignificant because of a lower enrollment, it does not necessarily mean that the effect does not exist.  A combination of outcome criteria, including objective (eg, magnetic resonance imaging or MRI) and more subjective measures (eg, clinical evaluation) may provide a stronger basis for results.  Data evaluation should include a report of the effect size to demonstrate a level of clinical importance as well as statistical significance.  In addition, because treatments are aimed at slowing or halting further nerve damage and functional decline, it is not expected that treatments will show reversal of existing damage or significant clinical improvement.  Instead, outcome measures typically describe a reduction in the number of attacks or in the progressive decline compared to other treatments or non-treatment. 

Therapies for the various types of MS have included immunosuppressive agents, immunomodulators, and anti-inflammatory medications.  The 2002 guidelines served as an evidence-base for the following summaries on the strongest recommendations for MS-targeted treatments:

  1. There was moderate to strong evidence that glucocorticoids may expedite recovery from acute attacks in MS.  Long-term administration of glucocorticoids and benefits remain unsupported.
  2. Treatment with Interferon-▀ (IFN▀) significantly reduces attack rates in both MS and patients deemed likely to develop MS through clinically isolated syndromes.  IFN▀ probably slows disability progression.  This led to a recommendation to consider IFN▀ in patients with RRMS, SPMS, or a high risk for developing clinically definite MS (CDMS).  There may be a dose-response curve or an effect of the frequency of administration.  There is a lack of evidence of any significant differences between the types of IFN▀ at this point except for the potential to promote neutralizing antibodies (NAb), which is correlated with the reduction in clinical effectiveness of IFN▀.  IFN▀-1a may have less potential to produce NAb than IFN▀-1b.  The differences between routes of administration (intramuscular vs. intravenous) are unknown.
  3. Glatiramer acetate (GA) can reduce attack rate in RRMS and can be considered for those patients.  While researchers have suggested that GA may have potential to slow progression there has been no strong evidence at this point.
  4. Cyclophosphamide has been proposed to provide some benefit for younger patients with progressive disease.  This is not currently supported.
  5. Weak evidence suggests a potential benefit of methotrexate in progressive disease.
  6. Azathioprine has had contentious results in reducing relapse rates and there is no data to suggest benefit in progressive disease.
  7. Cladribine may reduce gadolinium (Gd)-enhancing lesions in both relapsing and progressive MS but does not appear to alter attack rate or progression of disease.
  8. Patients with progressive disease may show a positive effect with cyclosporine.  However, the potential for adverse effects makes the risk unacceptable.
  9. Mitoxantrone shows some clinical benefits in reducing attack rates in relapsing MS.  This effect is outweighed by the risk for adverse effects.
  10. Intravenous immunoglobulin has lacked the evidence for a strong recommendation in either reducing attack rates in RRMS or of slowing decline in progressive MS.  There is a possibility that it may play a role in reducing attack rate if stronger evidence becomes available.
  11. There is little evidence to support the use of plasma exchange in MS other than one small study that used plasma exchange to treat acute episodes in patients without disability.
  12. Sulfasalazine has not shown therapeutic benefit.

This Journal Club will review recent studies that discuss treatments with IFN▀-1a (Avonex3 and Rebif4) and an investigations treatment with the humanized monoclonal antibody natalizumab (Antegren5). 


Click on the link at left to go to your desired page:  Introduction  Page 2  Page 3  Study 1  Study 2  Conclusion  Post-Test


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