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Predictive value of early brain atrophy on response in patients treated with interferon β.

Pérez-Miralles FC, Sastre-Garriga J, Vidal-Jordana A, Río J, Auger C, Pareto D, Tintoré M, Rovira A, Montalban X - Neurol Neuroimmunol Neuroinflamm (2015)

Bottom Line: Larger PBVC and WMVc% decreases were observed in patients with disability worsening at 4 years of follow-up, whereas no differences were found in BPVc% or GMVc%.Patients with decreases of PBVC and WMVc% below cutoff values were more prone to develop disability worsening (unadjusted hazard ratio [HR] 3.875, p = 0.005; HR 4.246, p = 0.004, respectively).PBVC (HR 4.751, p = 0.008) and the interaction of new T2 lesions with WMVc% (HR 1.086, p = 0.005) were found to be independent predictors of disability worsening in the multivariate analysis.

View Article: PubMed Central - PubMed

Affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.

ABSTRACT

Objective: To investigate the association between brain volume loss during the first year of interferon treatment and clinical outcome at 4 years.

Methods: Patients with multiple sclerosis initiating interferon β were clinically evaluated every 6 months for the presence of relapses and assessment of global disability using the Expanded Disability Status Scale (EDSS). MRI scans were performed at baseline and after 12 months, and the percentage of brain volume change (PBVC), brain parenchymal volume change (BPVc%), gray matter volume change (GMVc%), and white matter volume change (WMVc%) were estimated. Patients were divided based on the cutoff values for predicting confirmed EDSS worsening obtained by receiver operating characteristic analysis for all atrophy measurements. Survival curves and Cox proportional hazards regression to predict disability worsening at last observation were applied, adjusting for demographic, clinical, and radiologic variables.

Results: Larger PBVC and WMVc% decreases were observed in patients with disability worsening at 4 years of follow-up, whereas no differences were found in BPVc% or GMVc%. Cutoff points were obtained for PBVC (-0.86%; sensitivity 65.5%, specificity 71.4%) and WMVc% (-2.49%; sensitivity 85.3%, specificity 43.8%). Patients with decreases of PBVC and WMVc% below cutoff values were more prone to develop disability worsening (unadjusted hazard ratio [HR] 3.875, p = 0.005; HR 4.246, p = 0.004, respectively). PBVC (HR 4.751, p = 0.008) and the interaction of new T2 lesions with WMVc% (HR 1.086, p = 0.005) were found to be independent predictors of disability worsening in the multivariate analysis.

Conclusions: At the patient level, whole-brain and white matter volume changes in the first year of interferon β therapy are predictive of subsequent clinical evolution under treatment.

No MeSH data available.


Related in: MedlinePlus

Global brain and tissue-specific volume change rates (mean with 95% confidence interval)The p value from a one-sample t test is shown above each bar. Statistically significant differences in the intergroup analysis are linked with the p value shown above the connecting line. Gray bars represent results from the whole cohort. Light- colored bars represent patients without the feature indicated above (further attacks or confirmed Expanded Disability Status Scale [EDSS] worsening). Dark-colored bars represent patients with the feature indicated above (further attacks or confirmed EDSS worsening). % change: 100 × [first year volume − baseline volume]/[baseline volume]. Attacks = presence of further attacks after interferon β therapy; PBVC = percentage brain volume change; Worse = confirmed EDSS worsening.
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Figure 1: Global brain and tissue-specific volume change rates (mean with 95% confidence interval)The p value from a one-sample t test is shown above each bar. Statistically significant differences in the intergroup analysis are linked with the p value shown above the connecting line. Gray bars represent results from the whole cohort. Light- colored bars represent patients without the feature indicated above (further attacks or confirmed Expanded Disability Status Scale [EDSS] worsening). Dark-colored bars represent patients with the feature indicated above (further attacks or confirmed EDSS worsening). % change: 100 × [first year volume − baseline volume]/[baseline volume]. Attacks = presence of further attacks after interferon β therapy; PBVC = percentage brain volume change; Worse = confirmed EDSS worsening.

Mentions: Decreases were observed for PBVC (n = 105; mean −0.829%, SD 1.128, p < 0.001). Statistical Parametric Mapping 8–derived parameters (n = 84) showed decreases for BPV change (BPVc%) (mean −0.476%, SD 1.340, p = 0.002) and GMV change (GMVc%) (mean −0.727%, SD 2.123, p = 0.002) but not for WMV change (WMVc%) (mean −0.099%, SD 2.623, p = 0.730) (figure 1).


Predictive value of early brain atrophy on response in patients treated with interferon β.

Pérez-Miralles FC, Sastre-Garriga J, Vidal-Jordana A, Río J, Auger C, Pareto D, Tintoré M, Rovira A, Montalban X - Neurol Neuroimmunol Neuroinflamm (2015)

Global brain and tissue-specific volume change rates (mean with 95% confidence interval)The p value from a one-sample t test is shown above each bar. Statistically significant differences in the intergroup analysis are linked with the p value shown above the connecting line. Gray bars represent results from the whole cohort. Light- colored bars represent patients without the feature indicated above (further attacks or confirmed Expanded Disability Status Scale [EDSS] worsening). Dark-colored bars represent patients with the feature indicated above (further attacks or confirmed EDSS worsening). % change: 100 × [first year volume − baseline volume]/[baseline volume]. Attacks = presence of further attacks after interferon β therapy; PBVC = percentage brain volume change; Worse = confirmed EDSS worsening.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496631&req=5

Figure 1: Global brain and tissue-specific volume change rates (mean with 95% confidence interval)The p value from a one-sample t test is shown above each bar. Statistically significant differences in the intergroup analysis are linked with the p value shown above the connecting line. Gray bars represent results from the whole cohort. Light- colored bars represent patients without the feature indicated above (further attacks or confirmed Expanded Disability Status Scale [EDSS] worsening). Dark-colored bars represent patients with the feature indicated above (further attacks or confirmed EDSS worsening). % change: 100 × [first year volume − baseline volume]/[baseline volume]. Attacks = presence of further attacks after interferon β therapy; PBVC = percentage brain volume change; Worse = confirmed EDSS worsening.
Mentions: Decreases were observed for PBVC (n = 105; mean −0.829%, SD 1.128, p < 0.001). Statistical Parametric Mapping 8–derived parameters (n = 84) showed decreases for BPV change (BPVc%) (mean −0.476%, SD 1.340, p = 0.002) and GMV change (GMVc%) (mean −0.727%, SD 2.123, p = 0.002) but not for WMV change (WMVc%) (mean −0.099%, SD 2.623, p = 0.730) (figure 1).

Bottom Line: Larger PBVC and WMVc% decreases were observed in patients with disability worsening at 4 years of follow-up, whereas no differences were found in BPVc% or GMVc%.Patients with decreases of PBVC and WMVc% below cutoff values were more prone to develop disability worsening (unadjusted hazard ratio [HR] 3.875, p = 0.005; HR 4.246, p = 0.004, respectively).PBVC (HR 4.751, p = 0.008) and the interaction of new T2 lesions with WMVc% (HR 1.086, p = 0.005) were found to be independent predictors of disability worsening in the multivariate analysis.

View Article: PubMed Central - PubMed

Affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.

ABSTRACT

Objective: To investigate the association between brain volume loss during the first year of interferon treatment and clinical outcome at 4 years.

Methods: Patients with multiple sclerosis initiating interferon β were clinically evaluated every 6 months for the presence of relapses and assessment of global disability using the Expanded Disability Status Scale (EDSS). MRI scans were performed at baseline and after 12 months, and the percentage of brain volume change (PBVC), brain parenchymal volume change (BPVc%), gray matter volume change (GMVc%), and white matter volume change (WMVc%) were estimated. Patients were divided based on the cutoff values for predicting confirmed EDSS worsening obtained by receiver operating characteristic analysis for all atrophy measurements. Survival curves and Cox proportional hazards regression to predict disability worsening at last observation were applied, adjusting for demographic, clinical, and radiologic variables.

Results: Larger PBVC and WMVc% decreases were observed in patients with disability worsening at 4 years of follow-up, whereas no differences were found in BPVc% or GMVc%. Cutoff points were obtained for PBVC (-0.86%; sensitivity 65.5%, specificity 71.4%) and WMVc% (-2.49%; sensitivity 85.3%, specificity 43.8%). Patients with decreases of PBVC and WMVc% below cutoff values were more prone to develop disability worsening (unadjusted hazard ratio [HR] 3.875, p = 0.005; HR 4.246, p = 0.004, respectively). PBVC (HR 4.751, p = 0.008) and the interaction of new T2 lesions with WMVc% (HR 1.086, p = 0.005) were found to be independent predictors of disability worsening in the multivariate analysis.

Conclusions: At the patient level, whole-brain and white matter volume changes in the first year of interferon β therapy are predictive of subsequent clinical evolution under treatment.

No MeSH data available.


Related in: MedlinePlus