Contributions
Abstract: P584
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Background: Natalizumab (Tysabri), a humanized monoclonal antibody directed against a4-b1 integrin, is a leading immunomodulatory drug for the treatment of relapsing-remitting multiple sclerosis (RRMS) and is currently evaluated in in patients with secondary-progressive disease course.
Objectives: To assess longitudinal effects of Natalizumab, a humanized monoclonal antibody directed against a4-b1 integrin, on cortical gray matter thickness and cognitive performance in relapsing-remitting multiple sclerosis (RRMS) patients.
Methods: A longitudinal prospective study. RRMS patients underwent 3.0T 3D high resolution brain MRI (Signa, GE) examination and comprehensive computerized cognitive assessment before initiation of Natalizumab and at 2 years of treatment, along with neurological assessments once every 3 months. FreeSurfer 5.3 was applied to obtain brain morphometrics and to perform paired, longitudinal, cortical thickness analyses.
Results: Sixty RRMS patients, 44 Females, 16 Males, age 36.3 ± 9.3 years, disease duration 8.4 ± 6.0 years, expanded disability status scale (EDSS) score 2.6 ± 1.5, were included. Following 2 years of Natalizumab treatment, cortical thickness of the left hemisphere was stable (-0.7%, p=0.15), while the right hemisphere cortical thickness significantly decreased (-1.3% p=0.006). Surface based analysis demonstrated focal clusters of cortical gray matter atrophy (CGMA) at the parietal and frontal regions bilaterally with cluster wise probability p< 0.01. Patients who started Natalizumab treatment early (≤7.5 years from onset) exhibited no CGMA while those who initiated the treatment late (>7.5 years from onset) exhibited significant CGMA in five focal clusters on the right hemisphere and in one cluster in the left hemisphere, p< 0.02. Under 2 years of Natalizumab treatment cognitive performance was stable with significant improvement in information processing speed score (+3.7%, p=0.011).
Conclusions: We identified an early therapeutic window that is important to prevent CGMA in Natalizumab treated RRMS patients.
Disclosure: Lior Orbach - reports no disclosures.
Shmuel Miron - reports no disclosures.
Shay Menascu - Consulting fees (Genzyme), contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
David Magalshvili - Consulting fees (Genzyme), contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Mark Dolev - Consulting fees (Genzyme), contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Yael Stern - reports no disclosures.
Anat Achiron - Consulting fees (EMD Serono, Genzyme, Roche), contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Funding - No targeted funding was received to support this study.
Abstract: P584
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Background: Natalizumab (Tysabri), a humanized monoclonal antibody directed against a4-b1 integrin, is a leading immunomodulatory drug for the treatment of relapsing-remitting multiple sclerosis (RRMS) and is currently evaluated in in patients with secondary-progressive disease course.
Objectives: To assess longitudinal effects of Natalizumab, a humanized monoclonal antibody directed against a4-b1 integrin, on cortical gray matter thickness and cognitive performance in relapsing-remitting multiple sclerosis (RRMS) patients.
Methods: A longitudinal prospective study. RRMS patients underwent 3.0T 3D high resolution brain MRI (Signa, GE) examination and comprehensive computerized cognitive assessment before initiation of Natalizumab and at 2 years of treatment, along with neurological assessments once every 3 months. FreeSurfer 5.3 was applied to obtain brain morphometrics and to perform paired, longitudinal, cortical thickness analyses.
Results: Sixty RRMS patients, 44 Females, 16 Males, age 36.3 ± 9.3 years, disease duration 8.4 ± 6.0 years, expanded disability status scale (EDSS) score 2.6 ± 1.5, were included. Following 2 years of Natalizumab treatment, cortical thickness of the left hemisphere was stable (-0.7%, p=0.15), while the right hemisphere cortical thickness significantly decreased (-1.3% p=0.006). Surface based analysis demonstrated focal clusters of cortical gray matter atrophy (CGMA) at the parietal and frontal regions bilaterally with cluster wise probability p< 0.01. Patients who started Natalizumab treatment early (≤7.5 years from onset) exhibited no CGMA while those who initiated the treatment late (>7.5 years from onset) exhibited significant CGMA in five focal clusters on the right hemisphere and in one cluster in the left hemisphere, p< 0.02. Under 2 years of Natalizumab treatment cognitive performance was stable with significant improvement in information processing speed score (+3.7%, p=0.011).
Conclusions: We identified an early therapeutic window that is important to prevent CGMA in Natalizumab treated RRMS patients.
Disclosure: Lior Orbach - reports no disclosures.
Shmuel Miron - reports no disclosures.
Shay Menascu - Consulting fees (Genzyme), contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
David Magalshvili - Consulting fees (Genzyme), contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Mark Dolev - Consulting fees (Genzyme), contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Yael Stern - reports no disclosures.
Anat Achiron - Consulting fees (EMD Serono, Genzyme, Roche), contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Funding - No targeted funding was received to support this study.