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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

Comparison of survival curves based on confirmed Expanded Disability Status Scale worsening(A) According to the percentage brain volume change divided into 2 groups: ≤−0.86% (red line) or >−0.86% (black line). (B) According to the percentage of white matter volume change divided into 2 groups: ≤−2.49% (red line) or >−2.49% (black line).
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Figure 2: Comparison of survival curves based on confirmed Expanded Disability Status Scale worsening(A) According to the percentage brain volume change divided into 2 groups: ≤−0.86% (red line) or >−0.86% (black line). (B) According to the percentage of white matter volume change divided into 2 groups: ≤−2.49% (red line) or >−2.49% (black line).

Mentions: For PBVC, Kaplan-Meier curves (figure 2) up to 4 years showed an early separation of the event-free lines. Patients whose PBVC decreased below the −0.86% cutoff were more prone to develop CW during the 4 years of follow-up (unadjusted hazard ratio [HR] 3.875, 95% CI 1.5–10.0, p = 0.005). For WMVc%, Kaplan-Meier curves (figure 2) displayed similar results, indicating that patients losing more than 2.49% of WMV in the first year of interferon β therapy were more likely to develop confirmed EDSS increases during the 4 years of follow-up (unadjusted HR 4.246, 95% CI 1.27–9.20, p = 0.015).


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)

Comparison of survival curves based on confirmed Expanded Disability Status Scale worsening(A) According to the percentage brain volume change divided into 2 groups: ≤−0.86% (red line) or >−0.86% (black line). (B) According to the percentage of white matter volume change divided into 2 groups: ≤−2.49% (red line) or >−2.49% (black line).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Comparison of survival curves based on confirmed Expanded Disability Status Scale worsening(A) According to the percentage brain volume change divided into 2 groups: ≤−0.86% (red line) or >−0.86% (black line). (B) According to the percentage of white matter volume change divided into 2 groups: ≤−2.49% (red line) or >−2.49% (black line).
Mentions: For PBVC, Kaplan-Meier curves (figure 2) up to 4 years showed an early separation of the event-free lines. Patients whose PBVC decreased below the −0.86% cutoff were more prone to develop CW during the 4 years of follow-up (unadjusted hazard ratio [HR] 3.875, 95% CI 1.5–10.0, p = 0.005). For WMVc%, Kaplan-Meier curves (figure 2) displayed similar results, indicating that patients losing more than 2.49% of WMV in the first year of interferon β therapy were more likely to develop confirmed EDSS increases during the 4 years of follow-up (unadjusted HR 4.246, 95% CI 1.27–9.20, p = 0.015).

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