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. 2001;2001(4):CD002002.
doi: 10.1002/14651858.CD002002.

Interferon in relapsing-remitting multiple sclerosis

G P Rice  1 , B Incorvaia, L Munari, G Ebers, C Polman, R D'Amico, G Filippini
Affiliations

Interferon in relapsing-remitting multiple sclerosis

G P Rice et al. Cochrane Database Syst Rev. 2001.

Abstract

Background: Recombinant interferons have been shown to suppress both the clinical and magnetic resonance imaging (MRI) measures of disease activity in patients with relapsing remitting multiple sclerosis (RRMS).

Objectives: We performed a Cochrane review of all randomised, placebo-controlled trials of recombinant interferons in RRMS.

Search strategy: Of 208 articles identified by a predefined search strategy, seven of these, reporting randomised trials, met all the selection criteria and form the subject of this review.

Selection criteria: The trials selected were double-blind, placebo-controlled, randomised trials of RRMS patients who were treated with recombinant interferon, given by the subcutaneous or the intramuscular route.

Data collection and analysis: The quality of the trials was variable, with substantial methodological inadequacies in allocation concealment, high proportion and incomplete description of dropouts and failure to adhere to the principles of intention to treat analysis. The baseline characteristics were largely comparable between treatment and placebo groups. Because of prominent treatment-associated side effects, which could be easily identified by patients, these trials could be considered as single blind rather than double-blind.

Main results: Although 1215 patients were included in this review, only 919 (76%) contributed to the results concerning exacerbations and progression of the disease at two years. Specifically interferon significantly reduced the occurrence of exacerbations (RR =0.80, 95% CI [0.73,0.88], p<0.001) and progression of the disease (RR =0.69, 95% CI [0.55,0.87], p= 0.002) two years after randomisation. However, the correct assignment of dropouts was essential to the demonstration of efficacy, most conspicuously concerning the effect of the drug on disease progression. If interferon-treated patients who dropped out were deemed to have progressed (worst case scenario) the significance of these effects was lost (RR = 1.31, CI [0.60,2.89], p = 0.5). The evolution in magnetic resonance imaging (MRI) technology in the decade in which these trials were performed and different reporting of data among trials made it impossible to perform a quantitative analysis of the MRI results. Both clinical and laboratory side effects reported in the trials were more frequent in treated patients than in controls. No information was available regarding side effects and adverse events after two years of follow-up. The impact of interferon treatment (and its side effects) on the quality of life of patients was not reported in any trial included in this review.

Reviewer's conclusions: The efficacy of interferon on exacerbations and disease progression in patients with relapsing remitting MS was modest after one and two years of treatment. It was not possible to conduct a quantitative analysis beyond two years. Longer follow-up and more uniform reporting of clinical and MRI outcomes among these trials might have allowed for a more convincing conclusion.

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Conflict of interest statement

The review was assembled, analysed and reported independent from any pharmaceutical company input. Prof Rice has participated in clinical trials sponsored by SCHERING, SERONO, BERLEX, BIOGEN, and TEVA. He has received honoraria from these companies. Prof Ebers has received honoraria for lectures found to be sponsored by relevant companies and has been an investigator for several clinical trials in multiple sclerosis including three interferon studies involving SCHERING, SERONO funding. He does not feel his opinions (which are largely critical of the efficacy of interferons) are influenced by these associations. Prof Polman has received honoraria for lecturing, consultancy from companies producing interferon beta. Dr Filippini has received travel expenses from Farmades pharmaceutical company for participating at neurological conferences. Drs Munari, D'Amico, Incorvaia and Parmelli have no conflict of interest.

Figures

1.1
1.1. Analysis
Comparison 1 interferon versus placebo: primary outcomes, Outcome 1 Patients with at least one exacerbation until 1 yr.
1.2
1.2. Analysis
Comparison 1 interferon versus placebo: primary outcomes, Outcome 2 Patients with at least one exacerbation until 1 year: subgroup analysis.
1.3
1.3. Analysis
Comparison 1 interferon versus placebo: primary outcomes, Outcome 3 Patients with at least one exacerbation at 2 yrs.
1.4
1.4. Analysis
Comparison 1 interferon versus placebo: primary outcomes, Outcome 4 Patients with at least one exacerbation at 2 yrs (best scenario).
1.5
1.5. Analysis
Comparison 1 interferon versus placebo: primary outcomes, Outcome 5 Patients with at least one exacerbation at 2 yrs (worst scenario).
1.6
1.6. Analysis
Comparison 1 interferon versus placebo: primary outcomes, Outcome 6 Patients who progressed at 2 yrs.
1.7
1.7. Analysis
Comparison 1 interferon versus placebo: primary outcomes, Outcome 7 Patients who progressed at 2 yrs (best scenario).
1.8
1.8. Analysis
Comparison 1 interferon versus placebo: primary outcomes, Outcome 8 Patients who progressed at 2 yrs (worst scenario).
1.9
1.9. Analysis
Comparison 1 interferon versus placebo: primary outcomes, Outcome 9 Mean change in disability (EDSS) at 2 yrs.
2.1
2.1. Analysis
Comparison 2 Interferon versus placebo: secondary outcomes, Outcome 1 Patients who required steroid treatment until first year.
2.2
2.2. Analysis
Comparison 2 Interferon versus placebo: secondary outcomes, Outcome 2 Patients who required steroid treatment until 2 years.
2.3
2.3. Analysis
Comparison 2 Interferon versus placebo: secondary outcomes, Outcome 3 Patients with at least one hospital admission until 2 years.
3.1
3.1. Analysis
Comparison 3 interferon versus placebo: adverse events, Outcome 1 Patients who had clinical adverse events during treatment.
3.2
3.2. Analysis
Comparison 3 interferon versus placebo: adverse events, Outcome 2 Patients who had abnormal laboratory values during treatment.
See this image and copyright information in PMC

Comment in

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