Brain atrophy in natalizumab-treated patients: A 3-year follow-up.
BACKGROUND
A pseudoatrophy effect has been held responsible for the lack of net impact of natalizumab on brain volume outcomes in 2-year trials, but no data are available beyond 24 months.


OBJECTIVE
We aimed to investigate brain volume dynamics in natalizumab-treated patients in up to 3 years after therapy initiation with clinical correlations.


METHODS
Patients on natalizumab for at least 3 years were clinically assessed 3-monthly. Magnetic resonance imaging scans were performed at baseline and yearly. Brain volume changes were obtained with SIENA. Multivariate models were used to investigate the association between baseline inflammation and changes in brain volume and disability.


RESULTS
Sixty-two patients with multiple sclerosis were analysed. Mean age and disease duration were 34.7 (SD: 8.3) and 10.4 (SD: 6.6) years. Presence of gadolinium enhancement at baseline was not associated with Expanded Disability Status Scale changes (p=0.468), but was associated with larger brain volume decreases (p=0.005) in the first (p=0.024) and second year (p=0.019) but not in the third year (p=0.863). Brain volume changes at 12 and 36 months were marginally associated with disability status at month 12 (p=0.094) and 36 (p=0.084), respectively.


CONCLUSIONS
Baseline inflammation affects brain volume measures up to 24 months after natalizumab initiation. A marginal association of brain volume changes with disability is present.
Servei de Neurologia / Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain jsastre-garriga@cem-cat.org.
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Sastre-Garriga
Servei de Neurologia / Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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C
Tur
Unitat de Ressonància Magnètica (Servei de Radiologia), Hospital universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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D
Pareto
Servei de Neurologia / Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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A
Vidal-Jordana
Unitat de Ressonància Magnètica (Servei de Radiologia), Hospital universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Auger
Servei de Neurologia / Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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J
Río
Unitat de Ressonància Magnètica (Servei de Radiologia), Hospital universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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E
Huerga
Servei de Neurologia / Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Tintoré
Unitat de Ressonància Magnètica (Servei de Radiologia), Hospital universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Rovira
Servei de Neurologia / Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Montalban
D000328:Adult; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology*; D000069442:Natalizumab / Q000494:pharmacology*; D012720:Severity of Illness Index; D013997:Time Factors
D007155:Immunologic Factors; D000069442:Natalizumab
Multiple sclerosis; brain atrophy; brain volume; disability; natalizumab