Contributions
Abstract: EP1511
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: It is well known that the administration of interferon (IFN) beta-1a in patients with relapsing-remitting (RR) MS reduces brain lesion accumulation over time, as assessed by magnetic resonance imaging (MRI). It is less clear, however, whether such reduction may have treatment-specific spatio-temporal characteristics.
Objective: To assess spatio-temporal characteristics of active MRI lesions in patients treated with IFN beta-1a or placebo, by using a lesion mapping approach on monthly-acquired MRI data.
Methods: We performed a post-hoc analysis of MRI data in RRMS patients from the IMPROVE study, a randomized (2:1) clinical study (ClinicalTrials.gov identifier NCT00441103) comparing patients treated with IFN beta-1a 44 mcg given subcutaneously three times per week (n=120) versus placebo (n=60). We used MRI examinations acquired at weeks 4, 8, 12 and 16 to create lesion probability maps (LPMs) of the cumulative combined unique active (CUA) lesions in each patient group. At each time-point, differences in lesion location between treated and placebo groups were assessed along several white matter (WM) tracts by using predefined anatomic WM atlases. Differences in lesion frequency were assessed with a voxelwise comparison between treated and placebo groups within the general linear model framework and using nonparametric permutation test (p< 0.05, cluster-corrected).
Results: The progressive involvement of the WM area occupied by CUA lesions was half in the treated (41 cm3 at week 4, 95 cm3 at week 16, mean: 24 cm3/month) than in the placebo group (62 cm3 at week 4, 196 cm3 at week 16, mean: 48 cm3/month). Similar results were obtained with the WM tract analysis, with a reduction of lesion accumulation in the treated group in the order of 50% in the corticospinal tract (CST), 52% in the anterior thalamic radiation (ATR) and 65% in the superior longitudinal fascicle (SLF). At voxelwise analysis, LPM of the treated group showed lower frequency of CUA lesions than that of the placebo group since week 4. This became particularly pronounced at week 16 in the left CST (p< 0.005), left ATR (p< 0.005) and right SLF (p< 0.02).
Conclusions: Treatment with IFN beta-1a, in comparison to placebo, rapidly reduces lesion accumulation in RRMS patients along specific WM tracts, reaching the highest local differences in clinically eloquent WM tracts such as CST, SLF and ATR.
Disclosure: A. Giorgio, M. Battaglini, G. Gentile, M. L. Stromillo and A. Visconti have nothing to disclose
N De Stefano has received honoraria from Biogen-Idec, Genzyme, Merck Serono, Novartis, Roche and Teva for consulting services, speaking and travel support. He serves on advisory boards for Merck Serono, Novartis, Biogen-Idec, Roche, and Genzyme, he has received research grant support from the Italian MS Society
Abstract: EP1511
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: It is well known that the administration of interferon (IFN) beta-1a in patients with relapsing-remitting (RR) MS reduces brain lesion accumulation over time, as assessed by magnetic resonance imaging (MRI). It is less clear, however, whether such reduction may have treatment-specific spatio-temporal characteristics.
Objective: To assess spatio-temporal characteristics of active MRI lesions in patients treated with IFN beta-1a or placebo, by using a lesion mapping approach on monthly-acquired MRI data.
Methods: We performed a post-hoc analysis of MRI data in RRMS patients from the IMPROVE study, a randomized (2:1) clinical study (ClinicalTrials.gov identifier NCT00441103) comparing patients treated with IFN beta-1a 44 mcg given subcutaneously three times per week (n=120) versus placebo (n=60). We used MRI examinations acquired at weeks 4, 8, 12 and 16 to create lesion probability maps (LPMs) of the cumulative combined unique active (CUA) lesions in each patient group. At each time-point, differences in lesion location between treated and placebo groups were assessed along several white matter (WM) tracts by using predefined anatomic WM atlases. Differences in lesion frequency were assessed with a voxelwise comparison between treated and placebo groups within the general linear model framework and using nonparametric permutation test (p< 0.05, cluster-corrected).
Results: The progressive involvement of the WM area occupied by CUA lesions was half in the treated (41 cm3 at week 4, 95 cm3 at week 16, mean: 24 cm3/month) than in the placebo group (62 cm3 at week 4, 196 cm3 at week 16, mean: 48 cm3/month). Similar results were obtained with the WM tract analysis, with a reduction of lesion accumulation in the treated group in the order of 50% in the corticospinal tract (CST), 52% in the anterior thalamic radiation (ATR) and 65% in the superior longitudinal fascicle (SLF). At voxelwise analysis, LPM of the treated group showed lower frequency of CUA lesions than that of the placebo group since week 4. This became particularly pronounced at week 16 in the left CST (p< 0.005), left ATR (p< 0.005) and right SLF (p< 0.02).
Conclusions: Treatment with IFN beta-1a, in comparison to placebo, rapidly reduces lesion accumulation in RRMS patients along specific WM tracts, reaching the highest local differences in clinically eloquent WM tracts such as CST, SLF and ATR.
Disclosure: A. Giorgio, M. Battaglini, G. Gentile, M. L. Stromillo and A. Visconti have nothing to disclose
N De Stefano has received honoraria from Biogen-Idec, Genzyme, Merck Serono, Novartis, Roche and Teva for consulting services, speaking and travel support. He serves on advisory boards for Merck Serono, Novartis, Biogen-Idec, Roche, and Genzyme, he has received research grant support from the Italian MS Society