Short and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis

Xavier Armoiry, Alan Kan, G. J. Melendez-Torres, Rachel Court, P Sutcliffe, Peter Auguste, Jason Madan, Carl Counsell, A. Clarke

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Abstract

Background: Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short and long-term clinical effectiveness of these drugs in CIS.

Methods: We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies.

Results: We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR=0.64, 95%CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression.

Conclusions: Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.
Original languageEnglish
Pages (from-to)999-1009
Number of pages11
JournalJournal of Neurology
Volume265
Issue number5
Early online date22 Jan 2018
DOIs
Publication statusPublished - May 2018

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Interferon-beta
Multiple Sclerosis
Randomized Controlled Trials
Placebos
Pharmaceutical Preparations
Meta-Analysis
Glatiramer Acetate
Network Meta-Analysis
Databases

Keywords

  • Multiple sclerosis
  • clinically isolated syndrome
  • beta-interferon
  • glatiramer acetate
  • systematic review

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Short and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome : a systematic review of randomised controlled trials and network meta-analysis. / Armoiry, Xavier; Kan, Alan; Melendez-Torres, G. J.; Court, Rachel; Sutcliffe, P; Auguste, Peter; Madan, Jason; Counsell, Carl; Clarke, A.

In: Journal of Neurology, Vol. 265, No. 5, 05.2018, p. 999-1009.

Research output: Contribution to journalArticle

Armoiry, Xavier ; Kan, Alan ; Melendez-Torres, G. J. ; Court, Rachel ; Sutcliffe, P ; Auguste, Peter ; Madan, Jason ; Counsell, Carl ; Clarke, A. / Short and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome : a systematic review of randomised controlled trials and network meta-analysis. In: Journal of Neurology. 2018 ; Vol. 265, No. 5. pp. 999-1009.
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abstract = "Background: Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short and long-term clinical effectiveness of these drugs in CIS.Methods: We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies.Results: We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR=0.64, 95{\%}CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression.Conclusions: Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.",
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T1 - Short and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome

T2 - a systematic review of randomised controlled trials and network meta-analysis

AU - Armoiry, Xavier

AU - Kan, Alan

AU - Melendez-Torres, G. J.

AU - Court, Rachel

AU - Sutcliffe, P

AU - Auguste, Peter

AU - Madan, Jason

AU - Counsell, Carl

AU - Clarke, A.

N1 - Source of funding: This work is part of a larger report commissioned by the NIHR HTA Programme as project number ID809. A.C. and G.J.M.T. are partly supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care West Midlands at the University Hospitals Birmingham NHS Foundation Trust.

PY - 2018/5

Y1 - 2018/5

N2 - Background: Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short and long-term clinical effectiveness of these drugs in CIS.Methods: We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies.Results: We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR=0.64, 95%CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression.Conclusions: Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

AB - Background: Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short and long-term clinical effectiveness of these drugs in CIS.Methods: We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies.Results: We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR=0.64, 95%CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression.Conclusions: Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

KW - Multiple sclerosis

KW - clinically isolated syndrome

KW - beta-interferon

KW - glatiramer acetate

KW - systematic review

U2 - 10.1007/s00415-018-8752-8

DO - 10.1007/s00415-018-8752-8

M3 - Article

VL - 265

SP - 999

EP - 1009

JO - Journal of Neurology

JF - Journal of Neurology

SN - 0340-5354

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ER -