Composite MRI scores improve correlation with EDSS in multiple sclerosis

Poonawalla, Aziz H.; Datta, Sushmita; Juneja, Vaibhav; Nelson, Flavia; Wolinsky, Jerry S.; Cutter, Gary; Narayana, Ponnada A.

doi:10.1177/1352458510374892

Cited by 35 publications

(26 citation statements)

References 51 publications

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“…Z4 scores were constructed based on the addition of z-transformation of the Gd+ tissue volume, total lesion volume, T1-hypointense lesion volume and normalized CSF volume (1-BPF). 13,15 The numbers of enhanced lesions and UALs per MRI scan were compared among groups using a Poisson regression model with robust error variance. The model included total lesion numbers as response variables, and treatment group, EDSS strata, region, and either baseline number of enhanced lesions or UALs as covariates, and logtransformed number of scans as an offset variable.…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging outcomes from a phase III trial of teriflunomide

et al. 2013

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Objective: The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis (MS) pathology inferred by magnetic resonance imaging (MRI). Methods: Patients (n=1088) with relapsing MS were randomized to once-daily teriflunomide 7 mg or 14 mg, or placebo, for 108 weeks. MRI was recorded at baseline, 24, 48, 72 and 108 weeks. Annualized relapse rate and confirmed progression of disability (sustained ≥12 weeks) were the primary and key secondary outcomes. The principal MRI outcome was change in total lesion volume. Results: After 108 weeks, increase in total lesion volume was 67.4% (p=0.0003) and 39.4% (p=0.0317) lower in the 14 and 7 mg dose groups versus placebo. Other measures favoring teriflunomide were accumulated enhanced lesions, combined unique activity, T2-hyperintense and T1-hypointense component lesion volumes, white matter volume, and a composite MRI score; all were significant for teriflunomide 14 mg and most significant for 7 mg versus placebo. Conclusions: Teriflunomide provided benefits on brain MRI activity across multiple measures, with a dose effect evident on several markers. These effects were also consistent across selected subgroups of the study population. These findings complement clinical data showing significant teriflunomide-related reductions in relapse rate and disease progression, and demonstrate containment of MRI-defined disease progression.

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Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging outcomes from a phase III trial of teriflunomide

et al. 2013

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“…At first, it might seem counterintuitive that the combination can be greater than the sum of the two parts; however, such combinations of values have been used in other neurological disorders, including measures of disease severity in multiple sclerosis and Alzheimer’s disease. 16,20,21 In addition, as shown in our previous study, EIM and GSL only correlate moderately one with another, 13 and thus, likely provide distinct information about DMD pathology. Accordingly, combining the data sets logically might yield a measure with a stronger association with functional measures than either one alone.…”

Section: Discussionmentioning

confidence: 50%

“…Accordingly, here we study the concept of creating a composite measure of disease status by combining data from these two modalities, an approach that has been used with success in magnetic resonance imaging studies in multiple sclerosis. 15,16 This strategy has the potential to result in new, sensitive outcome measures that could be used in future clinical trials to facilitate drug development in DMD.…”

Section: Introductionmentioning

confidence: 99%

Composite Biomarkers for Assessing Duchenne Muscular Dystrophy: An Initial Assessment

Shklyar

Pasternak

Kapur

et al. 2015

Pediatric Neurology

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BACKGROUND Compared to individual parameters, composite biomarkers may provide a more effective means for monitoring disease progression and the effects of therapy in clinical trials than single measures. In this study, we built composite biomarkers for use in Duchenne muscular dystrophy (DMD) by combining values from two objective measures of disease severity: electrical impedance myography (EIM) and quantitative ultrasound (QUS) and evaluating how well they correlated to standard functional measures. METHODS Utilizing data from an ongoing study of EIM and QUS in 31 DMD and 26 healthy boys aged 2–14 years, we combined data sets by first creating z-scores based on the normal subject data and then using simple mathematical operations (addition and multiplication) to create composite measures. These composite scores were then correlated to age and standard measures of function including the six-minute walk test, the North Star Ambulatory Assessment (NSAA), and handheld dynamometry. RESULTS Combining data sets resulted in stronger correlations with all four outcomes than for either EIM or QUS alone in six of eight instances. These improvements reached statistical significance (p < 0.05) in several cases. For example, the correlation coefficient for the composite measure with the NSAA was 0.79 but was only 0.66 and 0.67 (respectively) for GSL and EIM separately. CONCLUSIONS Arithmetically derived composite scores can provide stronger correlations to functional measures than isolated biomarkers. Longitudinal study of such composite markers in DMD clinical trials is warranted.

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“…Several studies have suggested that GM atrophy who went on to experience clinical disease activity in the second and third year of therapy. 37 Composite MRI scores have also been shown to correlate more strongly with EDSS than do individual MRI measures and may prove to be important prognostic indicators in MS. 38 Improvements in MRI methodology and broader availability of instruments with more powerful 3-tesla magnets are increasing the accuracy of lesion detection and the ability to detect certain lesion types such as gray matter T 2 lesions. 36,39 One study 40 used an optimized MRI protocol incorporating 3-tesla MRI endpoints and monthly brain imaging to document MRI lesion evolution and to compare the efficacy of IFNβ-1b and glatiramer acetate (GA) for treatment of relapsing MS.…”

Section: ■■ Evolving Mri Methods For Improved Imaging In Msmentioning

confidence: 99%

Emerging Methods for Evaluating the Effectiveness of Intramuscular Interferon Beta-1a for Relapsing-Remitting Multiple Sclerosis

Foley¹,

Barnes²,

Nair³

2013

JMCP

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Newer outcome-based assessment methods have been developed that complement and improve upon the ability of historical clinical and magnetic resonance imaging (MRI) outcome measures to measure multiple sclerosis (MS) disease activity, patient functionality, treatment efficacy, and the risk of MS disease progression. These newer MS outcome assessments include instruments to evaluate cognitive function and patient quality of life; enhanced measures of disability, such as the Multiple Sclerosis Functional Composite instrument; and newer MRI measures of MS disease activity and neuronal changes, such as permanent T 1 hypointensities and central nervous system atrophy. When utilized in conjunction with standard MS outcome measures, these newer MS outcomes provide a more comprehensive picture of disease status and course and hold promise as tools for use in the development and testing of future MS therapies. The well-established first-line MS therapy intramuscular interferon beta-1a, which has been evaluated using a broad range of assessment methods, was used as a reference MS disease-modifying therapy to provide specific examples of studies utilizing newer evaluation methods. Utilization of evolving disease and assessment measures for patients with MS should improve MS patient diagnosis, treatment decisions, and monitoring of therapy. • Multiple sclerosis (MS) is a chronic, immune-mediated neurologic disease that is associated with progressive patient disability and diminished quality of life (QoL).• Historical clinical outcomes, such as MS relapses, physical disability measures, and magnetic resonance imaging (MRI) endpoints, do not capture important elements of MS, such as the impact of MS and MS therapies on a patient's perceived QoL.• This article provides an overview of several key newer MS patient outcomes, including instruments used to assess MS patient cognition, QoL, composite disability measures, and emerging MRI clinical endpoints.• Newer MS patient outcomes have the potential to improve MS patient care and the development and testing of future therapeutics for the treatment of MS. Summary Points Presented in this ArticleHowever, older measures do not capture the entire impact of the disease (e.g., cognition, upper limb function, etc.) on patient function and well-being. Newer outcome measures are being developed with the purpose of capturing additional aspects of the disease and facilitating a more comprehensive assessment of MS disability, progression, and therapeutic efficacy. The primary purpose of this article is to provide the managed care audience with an overview of the most prominent newer MS measures. The potential benefits of these newer outcomes are illustrated using published clinical data on intramuscular interferon beta-1a (IM IFNβ-1a) as an extensively evaluated, representative first-line MS therapy.

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Composite MRI scores improve correlation with EDSS in multiple sclerosis

Abstract: Background-Quantitative measures derived from MRI have been widely investigated as noninvasive biomarkers in multiple sclerosis (MS). However, the correlation of single measures with Expanded Disability Status Scale (EDSS) is poor, especially for studies with large population samples.

Cited by 35 publications

References 51 publications

Magnetic resonance imaging outcomes from a phase III trial of teriflunomide

Magnetic resonance imaging outcomes from a phase III trial of teriflunomide

Composite Biomarkers for Assessing Duchenne Muscular Dystrophy: An Initial Assessment

Emerging Methods for Evaluating the Effectiveness of Intramuscular Interferon Beta-1a for Relapsing-Remitting Multiple Sclerosis

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