Objective To compare the efficacy of fingolimod and natalizumab in preventing regional grey matter (GM) and white matter (WM) atrophy in relapsing-remitting multiple sclerosis (RRMS) over 2 years.
Methods Patients with RRMS starting fingolimod (n=25) or natalizumab (n=30) underwent clinical examination and 3T MRI scans at baseline (month (M) 0), M6, M12 and M24. Seventeen healthy controls were also scanned at M0 and M24. Tensor-based morphometry and SPM12 were used to assess the longitudinal regional GM/WM volume changes.
Results At M0, no clinical or GM/WM volume differences were found between treatment groups. At M24, both drugs reduced relapse rate (p<0.001 for both) and stabilised disability. At M6 vs M0, both groups experienced significant atrophy of several areas in the cortex, deep GM nuclei and supratentorial WM. Significant bilateral cerebellar GM and WM atrophy occurred in fingolimod patients only. At M12 vs M6 and M24 vs M12, further supratentorial GM and WM atrophy occurred in both groups. Bilateral GM/WM cerebellar atrophy continued to progress in fingolimod patients only. Compared with natalizumab, fingolimod-treated patients showed a significant cerebellar GM/WM atrophy, mainly at M6 vs M0, but still occurring up to M24. Compared with fingolimod, natalizumab-treated patients had a small number of areas of GM atrophy in temporo-occipital regions at the different time-points.
Conclusions Natalizumab and fingolimod are associated with heterogeneous temporal and regional patterns of GM and WM atrophy progression. Compared with natalizumab, fingolimod-treated patients experience accelerated GM and WM atrophy in the cerebellum, while both drugs show minimal regional volumetric differences in supratentorial regions.
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Contributors PP: drafting/revising the manuscript, MRI acquisition and analysis and interpretation of the data. MAR: drafting/revising the manuscript, study concept, MRI acquisition and analysis and interpretation of the data. EP and LS: drafting/revising the manuscript, MRI data postprocessing and interpretation of the data. LM and MR: patient enrolment and interpretation of the data. MF: drafting/revising the manuscript, study concept, MRI acquisition and analysis and interpretation of the data. He also acted as study supervisor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests Potential conflicts of interest outside the submitted work are as follows. PP received speakers honoraria from Biogen Idec, Novartis, Merck Serono and ExceMED. MAR received speakers honoraria from Biogen Idec, Novartis, Genzyme, Teva, Merck Serono, Roche, Celgene and Bayer and receives research support from the Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. LM has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi-Genzyme, Novartis, Teva, Merck-Serono, Biogen, Roche, Excemed. MF Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda and Teva Pharmaceutical Industries and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. The dataset used and analysed during the current study is available from the corresponding author on reasonable request.
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