Cladribine

RealLiving

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Multiple Sclerosis

New treatment guidelines outline diseasemodifying MS pharmacotherapy options.

FOR YEARS, ORGANIZATIONS such as the National Multiple Sclerosis Society have recommended treatment with disease-modifying medications for individuals with MS. New, evidence-based treatment guidelines now make specific recommendations for the available disease-modifying drugs, stressing the potential clinical strengths of each agent.

Published in Neurology,1" the guidelines were authored by the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Authors based their observations on the results of clinical trials in which the clinical utility of various disease-modifying agents were assessed for one or more of the four clinical courses of MS: relapsing-remitting, secondary progressive, primary progressive, and progressive-relapsing.

Structure of Recommendations Depending on the design of each reviewed clinical trial (with prospective, randomized, controlled clinical trials considered the most reliable and uncontrolled studies, case series, case reports, and expert opinions considered the least), the investigators rated each treatment as follows:

* "A" recommendations (A)-established as effective, ineffective, or harmful;

* "B" recommendations (B)-probably effective, ineffective, or harmful;

* "C" recommendations (C)-possibly effective, ineffective, or harmful;

* "U" recommendations (U)-Inadequate or conflicting data; given current knowledge, treatment is unproven.

Review of Recommendations

Glucocorticoids. According to the guideline panel, glucocorticoid (steroid) therapy may have short-term positive effects on "functional recovery speed," following acute MS exacerbations (A). No long-term benefits have been seen (B). Benefits do not appear to be influenced by drug formulation (the form in which the drug is administered; for example, orally, I.V., and so on), type of glucocorticoid, or dosage size (C). One prospective matched cohort study, however, showed that glucocorticoids may help in the long-term management of individuals with relapsing-remitting MS (C).

Interferon beta. Interferon beta has been shown to decrease the number of MS exacerbations (A), as well as reduce disease burden as measured by magnetic resonance imaging (B). It may also slow disease progression (B). Thus, interferon beta is a potentially appropriate therapy for patients "at high risk" of developing MS, and individuals with relapsingremitting MS and secondary-progressive MS marked with relapses (A). The agent may also be effective in individuals with secondaryprogressive MS who do not experience relapses (U).

A possible dose-response effect (the higher the dose, the greater the drug's benefit) has been seen with interferon beta (B). Drug formulation does not appear to play a role in its effectiveness, though it's a factor in terms of side effects (B). "There is no known clinical difference between the types of [interferon beta]," stated the authors, "although this has not been thoroughly studied."

Interferon beta treatment has been linked to the production of neutralizing antibodies (NAB) (A), which may reduce the drug's effectiveness (C). Production of NAB appears to occur less with interferon beta 1-a (Avonex) than with interferon beta 1-b (Betaseron).

Glatiramer acetate. Exacerbation rates in individuals with relapsing-remitting MS have been shown to decrease following treatment with glatiramer acetate (Copaxone) (A). The agent has also been shown to reduce disease severity, and may also slow disability progression (C). Glatiramer acetate treatment is thus recommended in any individual with relapsing-remitting MS (A). According to the authors, there is no conclusive evidence that the agent is beneficial in progressive forms of the disease (U).

Cyclophosphamide. The panel found pulse cyclophosphamide treatment ineffective in altering disease course in progressive MS (B).

Methotrexate. Limited data prompted the authors to describe methotrexate (various manufacturers) as an agent that potentially alters disease course in individuals with progressive MS (C).

Azathioprine. Azathioprine (various manufacturers) may reduce relapse rates in MS patients (C), but has not demonstrated efficacy in slowing progression to disability (U).

Cyclosporine. The results of one clinical trial showed potential benefit for cyclosporine (various manufacturers) in treating progressive forms of MS (C), although a poor side effect profile makes it an "unacceptable treatment," according to the authors (B).

Cladribine. Cladribine (Leustatin) does not appear to decrease exacerbation rates or slow disease progression (C).

Mitoxantrone. The panel stated that mitoxantrone (Novantrone) "probably" lowers exacerbation rates in individuals with relapsing MS, although its "potential toxicity ... may outweigh clinical benefits early in the course of the disease." (B). It may also slow disease progression (C).

Immune globulin intravenous (IGIV). Treatment with IGIV has potential benefit in terms of reducing rates of exacerbations in individuals with relapsing-remitting MS, although clinical trials have been hampered by small patient populations and incomplete data (C). It appears to have little effect on disease progression (C).

Sulfasalazine. Sulfasalazine (Azulfidine) did not show any benefit in MS patients, though this-conclusion is based on the results of a single study (B).

Further information regarding;the study, as well as more detailed analysis of the results, can be found at www.neurology.org.

Editors note: Only Avonex, Betaseron, Copaxone, and Novantrone are FDA approved for the treatment of MS. The remainder of the drugs are frequently used "off-label," or without FDA approval.

REFERENCES

1. Goodin DS, Frohman EM, Garmany GP, et al. Diseasemodifying therapies in multiple sclerosis: Report of the Therapeutic and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002; 58:169-178.

Copyright Springhouse Corporation Apr 2002
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