Open AccessThe 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
Author(s) -
Georgios Tsivgoulis,
Aristeidis H. Katsanos,
Dimitris Mavridis,
Nikolaos Grigoriadis,
Efthimios Dardiotis,
Ioannis Heliopoulos,
Panagiotis Papathanasopoulos,
Theodoros Karapanayiotides,
Constantinos Kilidireas,
Georgios M. Hadjigeorgiou,
Konstantinos Voumvourakis,
Helani
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0163296
Subject(s) - natalizumab , medicine , fingolimod , observational study , randomized controlled trial , placebo , multiple sclerosis , meta analysis , disease , pathology , immunology , alternative medicine
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; SMD indirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (OR indirect :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 (OR indirect = 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (OR indirect = 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.