Treatment of Multiple Sclerosis (MS) patients at a very early stage of the disease with recombinant interferon beta (IFN beta-1a and IFN beta-1b ) or glatiramer acetate (GA) could be useful in preventing irreversible damage in the central nervous system

Clerico M, Faggiano F, Palace J, Rice GP, Tintorè Subirana M, Durelli L

Published Online:

January 21, 2009

Treatment of relapsing-remitting Multiple Sclerosis (RRMS) is currently based on immunomodulatory drugs such as recombinant interferon (IFN beta-1a and IFN beta-1b) or glatiramer acetate (GA) although these therapies have been shown to be only modestly effective. Recently it has been suggested that the nervous damage, supported by inflammation processes, is an early event in MS evolution which immunomodulatory drugs can only partially prevent. IFN and GA demonstrated only partial efficacy that could be ascribed to the fact that in the studies that lead to their approval they have been initiated in patients with a disease history of several years. The objective of this review was to assess IFN beta and GA efficacy in preventing the conversion to clinically defined multiple sclerosis in patients after the first demyelinating events. Among the pertinent literature, only three studies were found to test the efficacy of IFN beta including a total of 1160 participants (639 under treatment, 521 under placebo); while no published study testing the efficacy of GA was found. The review found that early interferon beta-1a treatment is effective in preventing the conversion of the first isolated demyelinating episodes into clinically definite MS both after one year and two years of follow-up. Side effects and adverse events occurrence was the same as reported by the many studies on IFN beta treatments in MS patients with different levels of the disease. More research is however needed to evaluate the long term preventing efficacy of these drugs and dosages.

Abstract (click to read)

Background:

Immunomodulatory drugs have been shown to be only modestly effective in clinically definite relapsing remitting multiple sclerosis (RRMS). It has been hypothesized that their efficacy could be higher if used at the first appearance of symptoms, that is in the clinically isolated syndromes (CIS) suggestive of demyelinating events, a pathology which carries a high risk to convert to clinically definite MS (CDMS).

Objectives:

The objective of this review was to assess the effects of immunomodulatory drugs compared to placebo in adults in preventing conversion from CIS to CDMS which means the prevention of a second attack.

Search strategy:

We searched the Cochrane MS Group Trials Register (June 2007), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2007), MEDLINE (January 1966 to June 2007), EMBASE (January 1974 to June 2007) and reference lists of articles. We also contacted manufacturers and researchers in the field.

Selection criteria:

The trials selected were double-blind, placebo-controlled, randomised trials of CIS patients treated with immunomodulatory drugs.

Data collection and analysis:

Study selection have been independently done by two reviewers. Two further reviewers independently assessed trial quality and extracted and analysed data. Study authors were contacted for additional informations. Adverse effects information was collected from the trials.

Main results:

Only three trials tested the efficacy of interferon (IFN) beta including a total of 1160 participants (639 treatment, 521 placebo); no trial tested the efficacy of glatiramer acetate (GA). The metanalyses showed that the proportion of patients converting to CDMS was significantly lower in IFN beta-treated than in placebo-treated patients both after one year (pooled OR 0.53; 95% CI, 0.40 to 0.71; p <0.0001) as well as after two years of follow-up (pooled OR 0.52; 95% CI, 0.38 to 0.70; p <0.0001). Early treatment with IFN beta was associated with the side effect profile reported by the randomised controlled trials with this drug. Since side effects were reported with some heterogeneity in the three studies the metanalysis was possible only for the frequency of serious adverse events, not significantly different in IFN beta-treated or placebo-treated patients.

Authors' conclusions:

The efficacy of IFN beta treatment on preventing the conversion from CIS to CDMS was confirmed over two years of follow-up. Since patients had some clinical heterogeneity (length of follow-up, clinical findings of initial attack), it could be useful for the clinical practice to further analyse the efficacy of IFN beta treatment in different patient subgroups.

This record should be cited as:

Clerico M, Faggiano F, Palace J, Rice GP, Tintorè Subirana M, Durelli L. Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD005278. DOI: 10.1002/14651858.CD005278.pub3

Assessed as up to date:

July 18, 2007

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Primary Review Group:

Multiple Sclerosis and Rare Diseases of the Central Nervous System Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective are immunomodulatory drugs (glatiramer acetate or recombinant interferon beta) in preventing conversion from clinically isolated syndromes (CIS) to clinically definite multiple sclerosis (CDMS)?

Bottom line:

Compared to placebo, interferon beta is effective in preventing the conversion from CIS to CDMS (ie, prevention of a second attack) over 2 years of follow-up. There is no evidence delaying a second clinical or MRI detected attack has any effect on delaying disability outcomes.

Caveat:

Some limitations in the interpretation of the results are implied by analysis of the quality of the studies. In one trial no clear information about blinding of the investigators involved in treatment and evaluation is provided. In another trial the number of patients lost to follow-up during the second year is high (around 40%) due to early trial terminations. No trials tested the efficacy of glatiramer acetate.

Context:

Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system that most commonly affects women, with an onset typically between 20 and 40 years of age. It is the most common cause of neurological disability in young adults.

Cochrane Systematic Review:

Clerico M et al. Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis. Cochrane Reviews 2008, Issue 2. Article No. CD005278. DOI: 10.1002/14651858. CD005278.pub3. This review contains 3 trials involving 1160 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Neurology > Multiple sclerosis > Pharmacological treatments by drug type

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Treatment of Multiple Sclerosis (MS) patients at a very early stage of the disease with recombinant interferon beta (IFN beta-1a and IFN beta-1b ) or glatiramer acetate (GA) could be useful in preventing irreversible damage in the central nervous system

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