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Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis.
Cochrane Database Syst Rev. 2016 11 24; 11:CD009333.CD

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.

Authors+Show Affiliations

Unit of Neurorehabilitation - Multiple Sclerosis Center, I.R.C.C.S. Santa Maria Nascente - Fondazione Don Gnocchi, Via Capecelatro, 66, Milano, Italy, 20148.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

27880972

Citation

La Mantia, Loredana, et al. "Interferons-beta Versus Glatiramer Acetate for Relapsing-remitting Multiple Sclerosis." The Cochrane Database of Systematic Reviews, vol. 11, 2016, p. CD009333.
La Mantia L, Di Pietrantonj C, Rovaris M, et al. Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev. 2016;11:CD009333.
La Mantia, L., Di Pietrantonj, C., Rovaris, M., Rigon, G., Frau, S., Berardo, F., Gandini, A., Longobardi, A., Weinstock-Guttman, B., & Vaona, A. (2016). Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis. The Cochrane Database of Systematic Reviews, 11, CD009333.
La Mantia L, et al. Interferons-beta Versus Glatiramer Acetate for Relapsing-remitting Multiple Sclerosis. Cochrane Database Syst Rev. 2016 11 24;11:CD009333. PubMed PMID: 27880972.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis. AU - La Mantia,Loredana, AU - Di Pietrantonj,Carlo, AU - Rovaris,Marco, AU - Rigon,Giulio, AU - Frau,Serena, AU - Berardo,Francesco, AU - Gandini,Anna, AU - Longobardi,Anna, AU - Weinstock-Guttman,Bianca, AU - Vaona,Alberto, Y1 - 2016/11/24/ PY - 2016/11/24/pubmed PY - 2017/1/11/medline PY - 2016/11/24/entrez SP - CD009333 EP - CD009333 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev VL - 11 N2 - 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/27880972/Interferons_beta_versus_glatiramer_acetate_for_relapsing_remitting_multiple_sclerosis_ L2 - https://doi.org/10.1002/14651858.CD009333.pub3 DB - PRIME DP - Unbound Medicine ER -