Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

Giovannoni, Gavin; Cook, Stuart D.; Rammohan, Kottil; Rieckmann, Peter; Sørensen, Per Soelberg; Vermersch, Patrick; Hamlett, A; Viglietta, Vissia; Greenberg, Steven J.

doi:10.1016/s1474-4422(11)70023-0

Cited by 210 publications

(197 citation statements)

References 32 publications

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“…Its aetiology remains unknown and disease processes are still poorly understood. The observation that immunosuppressive treatment with cyclophosphamide (76), cladribine (77) or mitoxantrone (78) can limit disease activity suggested that MS is an immunologically mediated disease.…”

Section: Il-6 and Multiple Sclerosismentioning

confidence: 99%

IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?

Camporeale

Poli²

2012

Front Biosci

158

107

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Section: Il-6 and Multiple Sclerosismentioning

confidence: 99%

IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?

Camporeale

Poli²

2012

Front Biosci

158

107

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“…Indeed, "freedom from disease activity" assessed both clinically and using MRI is increasingly regarded as an optimal outcome by which to judge the effectiveness of therapy. 39,40 …”

Section: Background Historical Evolution Of Ms Diagnostic Criteriamentioning

confidence: 99%

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

Cook¹,

Dhib‐Jalbut²,

Dowling³

et al. 2012

International Journal of MS Care

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It has recently been suggested that the Lublin-Reingold clinical classification of multiple sclerosis (MS) be modified to include the use of magnetic resonance imaging (MRI). An international consensus conference sponsored by the Consortium of Multiple Sclerosis Centers (CMSC) was held from March 5to 7, 2010, to review the available evidence on the need for such modification of the Lublin-Reingold criteria and whether the addition of MRI or other biomarkers might lead to a better understanding of MS pathophysiology and disease course over time. The conference participants concluded that evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions (subclinical activity, subclinical relapses) should be added to the clinical classification of MS in distinguishing relapsing inflammatory from progressive forms of the disease. The consensus was that these changes to the classification system would provide more rigorous definitions and categorization of MS course, leading to better insights as to the evolution and treatment of MS. Int J MS Care. 2012;14:105-114. It was recently suggested by Lincoln et al. 1 that the Lublin-Reingold clinical classification of multiple sclerosis (MS) 2 for the assessment of MS phenotypes and patient evolution over time be modified to include magnetic resonance imaging (MRI). It was recommended that the classification incorporate the "conventional," generally available MRI techniques of gadolinium (Gd) T1-weighted sequences and dual-echo and fluid-attenuated inversion recovery (T2-weighted and FLAIR) images ( course over time and, in turn, more informed clinical trials and a better understanding of appropriate therapies.Prior to the meeting, a survey of members of the CMSC was conducted on the need to modify the Lublin-Reingold classification. Over a 1-week period, 141 responses were received, representing 16% of the CMSC members polled. The results were as follows: A total of 70% of respondents indicated that the LublinReingold classification did not sufficiently distinguish the different forms of MS; 87% felt that the LublinReingold classification did not sufficiently distinguish MS disease activity even within a given category of the disease; and 84% indicated that it would be useful to include certain subclinical indices of disease activity in the clinical classification, such as MRI gadoliniumother MRI modalities that are not currently widely available and other validated biomarkers might be added to the classification in the future.In response to the publication of Lincoln et al., 1 the Consortium of Multiple Sclerosis Centers (CMSC) sponsored an international consensus conference, which was held in Short Hills, New Jersey, from March 5 to 7, 2010. Participating in the conference were 28 invited MS experts from North and South America and Europe who were well versed in clinical trials, the management of MS, biostatistics, neuropathology, neuroimaging, and neuroimmunology. The goal of the meeting was to review the available...

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“…The DAF criteria are emerging as an increasingly important metric in recent clinical trials because they incorporate both radiographic and clinical measures of disease activity and are thought to possibly represent disease remission. 33,34 Particular combinations of transcripts that are predictive of IFNb response when measured before initiation of therapy were previously reported. 8 In that earlier report, the top classifier (CASP2, CASP10 and FLIP) achieved 87% predictive accuracy.…”

Section: Discussionmentioning

confidence: 90%

Prognostic biomarkers of IFNb therapy in multiple sclerosis patients

et al. 2014

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Background: Interferon beta (IFNb) reduces relapse frequency and disability progression in patients with multiple sclerosis (MS). Objectives: Early identification of prognostic biomarkers of IFNb-treated patients will allow more effective management of MS. Methods: The IMPROVE study evaluated subcutaneous IFNb versus placebo in 180 patients with relapsingremitting MS. Magnetic resonance imaging scans, clinical assessments, and blood samples were obtained at baseline and every 4 weeks from every participant. Thirty-nine biomarkers (32 transcripts; seven proteins) were studied in 155 patients from IMPROVE. Therapeutic response was defined by absence of new combined unique lesions, relapses, and sustained increase in Expanded Disability Status Scale over 1 year. A machine learning approach was used to examine the association between biomarker expression and treatment response. Results: While baseline levels of individual genes were relatively poor predictors, combinations of three genes were able to identify subjects with sub-optimal therapeutic responses. The triplet CASP2/IRF4/IRF6, previously identified in an independent dataset, was tested among other combinations. This triplet showed acceptable predictive accuracy (0.68) and specificity (0.88), but had relatively low sensitivity (0.22) resulting in an area under the curve (AUC) of 0.63. Other combinations of biomarkers resulted in AUC of up to 0.80 (e.g. CASP2/IL10/IL12Rb1). Conclusions: Baseline expression, or induction ratios, of specific gene combinations correlate with future therapeutic response to IFNb, and have the potential to be prognostically useful

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Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

Cited by 210 publications

References 32 publications

IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?

IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

Prognostic biomarkers of IFNb therapy in multiple sclerosis patients

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