The efficacy of Natalizumab versus Fingolimod for patients with relapsing-remitting multiple sclerosis

A systematic review, indirect evidence from randomized placebo-controlled trials and meta-analysis of observational head-to-head trials

Helani (Hellenic Academy Of Neuroimmunology)

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT). Methods and Findings: We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95% CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect= 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95% CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95% CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95% CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95% CI: from 1.15 to 4.18; p = z0.020). Conclusions: Indirect analyses of RCT data and head-to-head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation.

Original languageEnglish (US)
Article numbere0163296
JournalPloS one
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2016

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Relapsing-Remitting Multiple Sclerosis
systematic review
sclerosis
meta-analysis
placebos
Meta-Analysis
Randomized Controlled Trials
Placebos
relapse
randomized clinical trials
Recurrence
observational studies
Surface mount technology
Observational Studies
Natalizumab
Fingolimod Hydrochloride
therapeutics
Observation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

@article{6b1346ff203943c59ca58162b281f9d3,
title = "The efficacy of Natalizumab versus Fingolimod for patients with relapsing-remitting multiple sclerosis: A systematic review, indirect evidence from randomized placebo-controlled trials and meta-analysis of observational head-to-head trials",
abstract = "Background: Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT). Methods and Findings: We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95{\%} CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95{\%} CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect= 1.20;95{\%} CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95{\%} CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95{\%} CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95{\%} CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95{\%} CI: from 1.15 to 4.18; p = z0.020). Conclusions: Indirect analyses of RCT data and head-to-head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation.",
author = "{Helani (Hellenic Academy Of Neuroimmunology)} and Georgios Tsivgoulis and Katsanos, {Aristeidis H.} and Georgios Tsivgoulis and Nikolaos Grigoriadis and Efthymios Dardiotis and Ioannis Heliopoulos and Panagiotis Papathanasopoulos and Theodoros Karapanayiotides and Constantinos Kilidireas and Hadjigeorgiou, {Georgios M.} and Konstantinos Voumvourakis and Achilles Gravanis and Alexandros Papadimitriou and Anthony Rompos and Athanasia Mouzaki and Constantinos Kylintireas and Constantinos Voumvourakis and Domna Karagogeos and Georgios Hadjigeorgiou and Georgios Kollias and Ioannis Helliopoulos and Lesley Probert and Panagiotis Ioannidis and Pelidou, {Senate Errietta} and Socrates Tzartos and Theodoros Karapanagiotides and Villi Panoutsakopoulou",
year = "2016",
month = "9",
day = "1",
doi = "10.1371/journal.pone.0163296",
language = "English (US)",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - The efficacy of Natalizumab versus Fingolimod for patients with relapsing-remitting multiple sclerosis

T2 - A systematic review, indirect evidence from randomized placebo-controlled trials and meta-analysis of observational head-to-head trials

AU - Helani (Hellenic Academy Of Neuroimmunology)

AU - Tsivgoulis, Georgios

AU - Katsanos, Aristeidis H.

AU - Tsivgoulis, Georgios

AU - Grigoriadis, Nikolaos

AU - Dardiotis, Efthymios

AU - Heliopoulos, Ioannis

AU - Papathanasopoulos, Panagiotis

AU - Karapanayiotides, Theodoros

AU - Kilidireas, Constantinos

AU - Hadjigeorgiou, Georgios M.

AU - Voumvourakis, Konstantinos

AU - Gravanis, Achilles

AU - Papadimitriou, Alexandros

AU - Rompos, Anthony

AU - Mouzaki, Athanasia

AU - Kylintireas, Constantinos

AU - Voumvourakis, Constantinos

AU - Karagogeos, Domna

AU - Hadjigeorgiou, Georgios

AU - Kollias, Georgios

AU - Helliopoulos, Ioannis

AU - Probert, Lesley

AU - Ioannidis, Panagiotis

AU - Pelidou, Senate Errietta

AU - Tzartos, Socrates

AU - Karapanagiotides, Theodoros

AU - Panoutsakopoulou, Villi

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background: Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT). Methods and Findings: We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95% CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect= 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95% CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95% CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95% CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95% CI: from 1.15 to 4.18; p = z0.020). Conclusions: Indirect analyses of RCT data and head-to-head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation.

AB - Background: Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT). Methods and Findings: We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95% CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect= 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95% CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95% CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95% CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95% CI: from 1.15 to 4.18; p = z0.020). Conclusions: Indirect analyses of RCT data and head-to-head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation.

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U2 - 10.1371/journal.pone.0163296

DO - 10.1371/journal.pone.0163296

M3 - Article

VL - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e0163296

ER -