Contributions
Abstract: P798
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Brain volume (BV) loss, as measured by MRI-based computational methods, has proved clinical relevance as marker of neurodegeneration in several neurological conditions. In MS studies, the accelerated BV loss observed after initiation of some anti-inflammatory therapies, referred to as “pseudoatrophy”, complicates the interpretation of BV changes.
Objective: To assess the dynamics of pseudoatrophy in RRMS patients treated with Interferon (IFN) beta-1a or placebo, by using monthly MRI data
Methods: We performed a post-hoc analysis of MRI data of 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 s.c. 3 times/week (n=120) versus placebo (n=60). We used the SIENA-XL method (fsl.fmrib.ox.ac.uk) on the T1-weighted images acquired at weeks 0, 4, 8 12 and 16 in order to compare differences in percentage of grey matter volume change (PGMVC) and white matter volume change (PWMVC) between the two study arms. In the treatment arm, data acquired at week 20, 24, 28, 32, 36 and 40 were used to assess the slope of changes over the whole treatment period. The slopes of PGMVC and PWMVC over time were estimated by using a mixed effect linear model. A treatment-by-time interaction term was used to assess whether the slope of changes was different according to the study arm. In the IFN-treated arm, a quadratic term was included in the model to evaluate a plateauing effect over the 40-weeks treatment.
Results: Up to week 16, PGMVC was -0.14%/month in the placebo group and -0.27%/ month in the treated group (p< 0.001). Over the same period, the decrease in PWMVC was -0.067%/month in the placebo group and -0.116%/month in the treatment group (p=0.27). In the treatment group, over 40 weeks the decrease in PGMVC showed a significant (p< 0.001) quadratic component, indicating PGMVC plateauing. This was estimated (by checking the time of maximum slope) to start at week 20. Over the same time period, the small decreases in PWMVC showed only a trend (p=0.06) for a quadratic slope with a plateau starting at week 20.
Conclusions: In monthly MRI data, RRMS patients treated with IFN beta-1a showed more pronounced pseudoatrophy effect in the GM than WM compartment, with a maximum decrease up to week 20. These results can be helpful to factor out the confounding volumetric effects of anti-inflammatory therapies and thus measuring BV loss more accurately.
Disclosure: M. Battaglini, A. Giorgio, L. Luchetti, M. L. Stromillo, A. Visconti have nothing to disclose
M.P. Sormani has received personal compensation for consulting services and for speaking activities from Genzyme, Merck Serono, Teva, Synthon, Actelion, Novartis and Biogen Idec.
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: P798
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Brain volume (BV) loss, as measured by MRI-based computational methods, has proved clinical relevance as marker of neurodegeneration in several neurological conditions. In MS studies, the accelerated BV loss observed after initiation of some anti-inflammatory therapies, referred to as “pseudoatrophy”, complicates the interpretation of BV changes.
Objective: To assess the dynamics of pseudoatrophy in RRMS patients treated with Interferon (IFN) beta-1a or placebo, by using monthly MRI data
Methods: We performed a post-hoc analysis of MRI data of 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 s.c. 3 times/week (n=120) versus placebo (n=60). We used the SIENA-XL method (fsl.fmrib.ox.ac.uk) on the T1-weighted images acquired at weeks 0, 4, 8 12 and 16 in order to compare differences in percentage of grey matter volume change (PGMVC) and white matter volume change (PWMVC) between the two study arms. In the treatment arm, data acquired at week 20, 24, 28, 32, 36 and 40 were used to assess the slope of changes over the whole treatment period. The slopes of PGMVC and PWMVC over time were estimated by using a mixed effect linear model. A treatment-by-time interaction term was used to assess whether the slope of changes was different according to the study arm. In the IFN-treated arm, a quadratic term was included in the model to evaluate a plateauing effect over the 40-weeks treatment.
Results: Up to week 16, PGMVC was -0.14%/month in the placebo group and -0.27%/ month in the treated group (p< 0.001). Over the same period, the decrease in PWMVC was -0.067%/month in the placebo group and -0.116%/month in the treatment group (p=0.27). In the treatment group, over 40 weeks the decrease in PGMVC showed a significant (p< 0.001) quadratic component, indicating PGMVC plateauing. This was estimated (by checking the time of maximum slope) to start at week 20. Over the same time period, the small decreases in PWMVC showed only a trend (p=0.06) for a quadratic slope with a plateau starting at week 20.
Conclusions: In monthly MRI data, RRMS patients treated with IFN beta-1a showed more pronounced pseudoatrophy effect in the GM than WM compartment, with a maximum decrease up to week 20. These results can be helpful to factor out the confounding volumetric effects of anti-inflammatory therapies and thus measuring BV loss more accurately.
Disclosure: M. Battaglini, A. Giorgio, L. Luchetti, M. L. Stromillo, A. Visconti have nothing to disclose
M.P. Sormani has received personal compensation for consulting services and for speaking activities from Genzyme, Merck Serono, Teva, Synthon, Actelion, Novartis and Biogen Idec.
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