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Meta-Analysis
. 2016 Nov 24;11(11):CD009333.
doi: 10.1002/14651858.CD009333.pub3.

Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis

Loredana La Mantia  1 , Carlo Di Pietrantonj, Marco Rovaris, Giulio Rigon, Serena Frau, Francesco Berardo, Anna Gandini, Anna Longobardi, Bianca Weinstock-Guttman, Alberto Vaona
Affiliations
Meta-Analysis

Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis

Loredana La Mantia et al. Cochrane Database Syst Rev. .

Abstract

Background: Interferons-beta (IFNs-beta) and glatiramer acetate (GA) were the first two disease-modifying therapies (DMTs) approved 20 years ago for the treatment of multiple sclerosis (MS). DMTs' prescription rates as first or switching therapies and their costs have both increased substantially over the past decade. As more DMTs become available, the choice of a specific DMT should reflect the risk/benefit profile, as well as the impact on quality of life. As MS cohorts enrolled in different studies can vary significantly, head-to-head trials are considered the best approach for gaining objective reliable data when two different drugs are compared. The purpose of this systematic review is to summarise available evidence on the comparative effectiveness of IFNs-beta and GA on disease course through the analysis of head-to-head trials.This is an update of the Cochrane review 'Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis' (first published in the Cochrane Library 2014, Issue 7).

Objectives: To assess whether IFNs-beta and GA differ in terms of safety and efficacy in the treatment of people with relapsing-remitting (RR) MS.

Search methods: We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (08 August 2016) and the reference lists of retrieved articles. We contacted authors and pharmaceutical companies.

Selection criteria: Randomised controlled trials (RCTs) comparing directly IFNs-beta versus GA in study participants affected by RRMS.

Data collection and analysis: We used standard methodological procedures as expected by Cochrane.

Main results: Six trials were included and five trials contributed to this review with data. A total of 2904 participants were randomly assigned to IFNs (1704) and GA (1200). The treatment duration was three years for one study, two years for the other four RCTs while one study was stopped early (after one year). The IFNs analysed in comparison with GA were IFN-beta 1b 250 mcg (two trials, 933 participants), IFN-beta 1a 44 mcg (three trials, 466 participants) and IFN-beta 1a 30 mcg (two trials, 305 participants). Enrolled participants were affected by active RRMS. All studies were at high risk for attrition bias. Three trials are still ongoing, one of them completed.Both therapies showed similar clinical efficacy at 24 months, given the primary outcome variables (number of participants with relapse (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.87 to 1.24) or progression (RR 1.11, 95% CI 0.91 to 1.35). However at 36 months, evidence from a single study suggests that relapse rates were higher in the group given IFNs than in the GA group (RR 1.40, 95% CI 1.13 to 1.74, P value 0.002).Secondary magnetic resonance imaging (MRI) outcomes analysis showed that effects on new or enlarging T2- or new contrast-enhancing T1 lesions at 24 months were similar (mean difference (MD) -0.15, 95% CI -0.68 to 0.39, and MD -0.14, 95% CI -0.30 to 0.02, respectively). However, the reduction in T2- and T1-weighted lesion volume was significantly greater in the groups given IFNs than in the GA groups (MD -0.58, 95% CI -0.99 to -0.18, P value 0.004, and MD -0.20, 95% CI -0.33 to -0.07, P value 0.003, respectively).The number of participants who dropped out of the study because of adverse events was similar in the two groups (RR 0.95, 95% CI 0.64 to 1.40).The quality of evidence for primary outcomes was judged as moderate for clinical end points, but for safety and some MRI outcomes (number of active T2 lesions), quality was judged as low.

Authors' conclusions: The effects of IFNs-beta and GA in the treatment of people with RRMS, including clinical (e.g. people with relapse, risk to progression) and MRI (Gd-enhancing lesions) measures, seem to be similar or to show only small differences. When MRI lesion load accrual is considered, the effect of the two treatments differs, in that IFNs-beta were found to limit the increase in lesion burden as compared with GA. Evidence was insufficient for a comparison of the effects of the two treatments on patient-reported outcomes, such as quality-of-life measures.

PubMed Disclaimer

Conflict of interest statement

This Cochrane review has no commercial sponsorship.

MR and BWG have participated in meetings and trials sponsored by large pharmaceutical companies.

LLM, SF, AG, FB, GR, AL, CDP, and AV have no conflicts of interest.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Number of participants who experienced at least 1 relapse at 24 months and at end of follow‐up, Outcome 1 At the end of follow‐up (24 ‐ 36 months).
1.2
1.2. Analysis
Comparison 1 Number of participants who experienced at least 1 relapse at 24 months and at end of follow‐up, Outcome 2 During follow‐up likely scenario.
2.1
2.1. Analysis
Comparison 2 Number of participants who worsened during the study (EDSS progression) at 24 months and at the end of follow‐up, Outcome 1 At the end of follow‐up (24‐36 months).
2.2
2.2. Analysis
Comparison 2 Number of participants who worsened during the study (EDSS progression) at 24 months and at the end of follow‐up, Outcome 2 During follow‐up likely scenario.
3.1
3.1. Analysis
Comparison 3 Number of participants who withdrew or dropped out of the study because of adverse events, Outcome 1 Number of participants who dropped out for AE.
3.2
3.2. Analysis
Comparison 3 Number of participants who withdrew or dropped out of the study because of adverse events, Outcome 2 Number of participants who dropped out for SAE.
4.1
4.1. Analysis
Comparison 4 Frequency of relapse (ARR), Outcome 1 Relapse frequency.
5.1
5.1. Analysis
Comparison 5 Time to first relapse, Outcome 1 Time to first relapse (HR).
7.1
7.1. Analysis
Comparison 7 Number of participants treated with steroids for MS relapse, Outcome 1 Patients Treated with Steroids.
9.1
9.1. Analysis
Comparison 9 Mean number of active (new or enlarged) T2‐hyperintense lesions per participant at 6 ‐ 12 ‐ 24 months and at end of follow‐up period, Outcome 1 During follow‐up.
10.1
10.1. Analysis
Comparison 10 Mean number of new contrast‐enhancing T1 lesions per participant at 6 ‐ 12 ‐ 24 months and at end of follow‐up period, Outcome 1 Mean number.
11.1
11.1. Analysis
Comparison 11 Mean change in total T2‐hyperintense lesion load at 12‐24 months and at end of follow‐up period, Outcome 1 Mean absolute change.
12.1
12.1. Analysis
Comparison 12 Mean change in total T1‐hypointense lesion load at 12‐24 months and at end of follow‐up, Outcome 1 Mean absolute change.
13.1
13.1. Analysis
Comparison 13 Mean change in total brain volume (as a measure of atrophy) at 12‐24 months and at end of follow‐up, Outcome 1 Mean absolute change.
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References

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EUCTR2012‐003735‐32‐GR {unpublished data only}
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References to other published versions of this review

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