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.
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).


RESULTS
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.
Second Department of Neurology, "Attikon" Hospital, School of Medicine, University of Athens, Athens, Greece.|Department of Neurology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.|International Clinical Research Center, Department of Neurology, St. Anne's University Hospital in Brno, Brno, Czech Republic.
Georgios
G
Tsivgoulis
Second Department of Neurology, "Attikon" Hospital, School of Medicine, University of Athens, Athens, Greece.|Department of Neurology, School of Medicine, University of Ioannina, Ioannina, Greece.
Aristeidis H
AH
Katsanos
Department of Primary Education, University of Ioannina, Ioannina, Greece.|Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
Dimitris
D
Mavridis
Second Department of Neurology, "AHEPA" University Hospital, Aristotelion University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Nikolaos
N
Grigoriadis
Department of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece.
Efthymios
E
Dardiotis
Department of Neurology, Alexandroupolis University Hospital, Democritus University of Thrace, Alexandroupolis, Greece.
Ioannis
I
Heliopoulos
Department of Neurology, University of Patras Medical School, Patras, Greece.
Panagiotis
P
Papathanasopoulos
Second Department of Neurology, "AHEPA" University Hospital, Aristotelion University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Theodoros
T
Karapanayiotides
First Department of Neurology, "Eginition" Hospital, School of Medicine, University of Athens, Athens, Greece.
Constantinos
C
Kilidireas
Department of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece.
Georgios M
GM
Hadjigeorgiou
Second Department of Neurology, "Attikon" Hospital, School of Medicine, University of Athens, Athens, Greece.
Konstantinos
K
Voumvourakis
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