Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis

Dalton, Catherine M.; Miszkiel, Katherine; Barker, Gareth J.; MacManus, David; Pepple, Tracy I; Panzara, Michael A.; Yang, Minhua; Hulme, Allison; O’Connor, Paul; Miller, David H.

doi:10.1007/s00415-004-0332-4

Cited by 121 publications

(72 citation statements)

References 21 publications

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“…lesions that evolved to T1-hypointense lesions was 15% (vs. 25% in the placebo group, p = 0.045) and the OR of evolution from Gd? to T1-hypointense lesions was 0.48 (95% CI 0.24, 0.94; p = 0.031) [14]. Glatiramer acetate has also been shown to reduce the evolution of Gd?…”

Section: Discussionmentioning

confidence: 97%

“…Similar to BG-12, some currently approved MS disease-modifying therapies affect the evolution of Gd? lesions to T1-hypointense lesions [14,19]. In patients treated with natalizumab, the proportion of Gd?…”

Section: Discussionmentioning

confidence: 99%

“…lesions were classified as large ([5 mm) or small (B5 mm) based on measurement of their largest diameter. This cutoff criterion ([5 mm and B5 mm) was chosen for this analysis because it was used in similar analyses for other MS therapeutics [13,14]. The status of the new Gd?…”

Section: Mri Analysismentioning

confidence: 99%

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BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis

et al. 2010

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BG-12, an immunomodulatory agent, reduces frequency of new gadolinium-enhancing (Gd?) lesions in relapsing multiple sclerosis (MS). This study reports the effect of 240 mg BG-12 orally three times daily (tid) for 24 weeks on the evolution of new Gd? lesions to T1-hypointense lesions. Brain magnetic resonance imaging (MRI) scans from patients in placebo and 240 mg BG-12 tid arms of a phase 2b study were examined retrospectively. Included patients had at least one new Gd? lesion from weeks 4 to 12. Week 24 scans were analyzed for number and proportion of new Gd? lesions that evolved to T1-hypointense lesions. Eighteen patients receiving BG-12 and 38 patients receiving placebo were included in the analysis. The analysis tracked 147 new Gd? lesions in patients from the BG-12 group and 221 Gd? lesions in patients from the placebo group. The percentage of Gd? lesions that evolved to T1-hypointense lesions was 34% lower with BG-12 treatment versus placebo (29%, BG-12; 44%, placebo; odds ratio 0.51; 95% confidence interval 0.43, 0.61; p \ 0.0001). In addition toElectronic supplementary material The online version of this article

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis

et al. 2010

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“…A reduction in such evolution can be considered as the surrogate marker for improved recovery from acute relapses (i.e., there is less residual axonal loss due to acute inflammation). Such a treatment effect has been demonstrated for glatiramer acetate 96 and natalizumab 97 but not ␤-interferon. 98 …”

Section: T1 Hypointense Lesionsmentioning

confidence: 94%

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Miller¹

2004

Neurotherapeutics

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Summary:Multiple sclerosis (MS) is a chronic disease of the CNS that most commonly affects young adults. It is usually characterized in the early years by acute relapses followed by partial or complete remission; in later years progressive and irreversible disability develops. Because of the protracted and unpredictable clinical course, biological surrogate markers are much needed to make clinical trials of potential disease-modifying treatments more efficient. Magnetic resonance (MR) outcome measures are now widely used to monitor treatment outcome in MS trials. Areas of multifocal inflammation are detected with a high sensitivity as new areas of gadolinium enhancement and T2 abnormality, and these may be considered as surrogate markers for clinical relapses. However, progressive disability is not clearly related to inflammatory lesions but rather to a progressive and diffuse process with increasing neuroaxonal loss. MR surrogate measures for neuroaxonal loss include atrophy (tissue loss in brain and spinal cord), N-acetyl aspartate, and T1 hypointense lesions. Diffuse abnormality in normal appearing brain tissue may also be monitored using magnetization transfer ratio and other quantitative MR measures. For treatment trials of new agents aimed at preventing disability, measures of neuroaxonal damage should be acquired, especially atrophy, which occurs at all stages of MS and which can be quantified in a sensitive and reproducible manner. Because the MR surrogates for neuroaxonal loss are not yet validated as predicting future disability, definitive trials should continue to monitor an appropriate disability endpoint.

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“…93 Enhancements that formed despite treatment with glatiramer acetate (GA) were less likely to persist over time as T1-hypointense lesions, as compared to placebotreated patients. 8 In a recent trial, 94 enhancements that developed despite therapy with natalizumab were much less likely to be found 6 -11 months later, often in the absence of continued drug exposure (odds ratio 0.48 [CI 0.24 -0.94]). In the case of GA, this may be due to improved lesion resolution.…”

Section: Hypointense Lesions On T1-weighted Imagesmentioning

confidence: 99%

Imaging of multiple sclerosis: Role in neurotherapeutics

Bakshi¹,

Minagar²,

Jaisani³

et al. 2005

Neurotherapeutics

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Summary:Magnetic resonance imaging (MRI) plays an everexpanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normalappearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1-or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics.

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Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis

Cited by 121 publications

References 21 publications

BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis

BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Imaging of multiple sclerosis: Role in neurotherapeutics

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