Multiple Sclerosis: Rituximab Had Better Short and Medium Term Outcomes

MedicalResearch.com Interview with:
Fredrik Piehl MD PhD, prof. of Neurology

Neuroimmunology Unit. Dept Clinical Neuroscience
Neurology Dept.
Karolinska University Hospital (Solna)
Stockholm

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years we have seen a drastic increase in treatment options for relapsing-remitting multiple sclerosis (RRMS). However, it is difficult to deduce long term performance of different drugs based only on data from randomized controlled trials, since such trials are performed in selected patients without major co-morbidities and perhaps also enriched for those with a milder disease course. In addition, most trials only last for two years and lack relevant comparators. This lack of knowledge makes it difficult to predict if a drug will work or not for a given patient, in turn leading to frequent treatment switches but also different treatment practices across countries, regions or even between centers. This is also the case in Sweden, but with the additional aspect that some regions have opted to treat most newly diagnosed RRMS patients with rituximab (Rituxan/Mabthera), a drug not formally approved for RRMS, but with extensive safety data from other indications.

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Multiple Sclerosis Patients Show Cognitive Benefit From Remotely Supervised Transcranial Direct Current Stimulation

MedicalResearch.com Interview with:

Leigh E. Charvet, PhD Associate Professor, Department of Neurology Department of Neurology New York University Langone Medical Center New York, NY

Dr. Charvet

Leigh E. Charvet, PhD
Associate Professor, Department of Neurology
Department of Neurology
New York University Langone Medical Center
New York, NY

MedicalResearch.com: What is the background for transcranial direct current stimulation? What are the main findings of this study in multiple sclerosis patients?

Response: The application of tDCS is a relatively recent therapeutic development that utilizes low amplitude direct currents to induce changes in cortical excitability. When paired with a rehabilitation activity, it may improve learning rates and outcomes.

Multiple repeated sessions are needed for both tDCS and cognitive training sessions to see a benefit. Because it is not feasible to have participants come to clinic daily for treatments, we developed a method to deliver tDCS paired with cognitive training (using computer-based training games) to patients at home. Our protocol uses a telemedicine platform with videoconferencing to assist study participants with all the procedures and to ensure safety and consistency across treatment sessions.

When testing our methods, we enrolled 25 participants with multiple sclerosis (MS) completed 10 sessions of tDCS (2.0 mA x 20 minutes, dorsolateral prefrontal cortex, left anodal) using the remotely-supervised telerehabilitation protocol. This group was compared to n=20 MS participants who completed 10 sessions of cognitive training only (also through remote supervision).

We administered cognitive testing measures at baseline and study end. We found that both the tDCS and cognitive training only group had similar and slight improvements on composites of standard neuropsychological measures and basic attention. However, the tDCS group had a significantly greater gain on computer-based measures of complex attention and on a measure of intra-individual variability in response times.

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Multiple Treatment Options Now Available for Multiple Sclerosis

MedicalResearch.com Interview with:

Tomas Kalincik, MD, PhD, PGCertBiostat Neurologist and Senior Research Fellow Melbourne Brain Centre | Department of Medicine | University of Melbourne Department of Neurology | Royal Melbourne Hospital Melbourne | Victoria | Australia

Dr. Tomas Kalincik

Tomas Kalincik, MD, PhD, PGCertBiostat
Neurologist and Senior Research Fellow
Melbourne Brain Centre | Department of Medicine | University of Melbourne
Department of Neurology | Royal Melbourne Hospital
Melbourne | Victoria | Australia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Multiple sclerosis is a disease predominantly of young adults, with the peak of incidence in the 3rd and 4th decades. It is the most common cause of neurological disability in young adults. Only in Australia, 23,000 people are living with MS, with MS representing an annual cost of almost 1 billion $AU to the Australian society. It is a disease that presents with broad range of neurological symptoms and signs, which are typically temporary (these are called relapses) that with time can lead to permanent neurological disability. While there is currently no cure for MS, with appropriate therapy, its symptoms can be controlled and the disability progression slowed down.

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CSF Biomarker May Signal Progression of Clinically Isolated Syndrome to MS

MedicalResearch.com Interview with:

Prof Rogier Q Hintzen Neurologist/immunologist Head MS Centre ErasMS Dept of Neurology Erasmus MC, PB 2040 Rotterdam

Prof Rogier Q Hintzen

Prof Rogier Q Hintzen
Neurologist/immunologist
Head MS Centre ErasMS
Dept of Neurology
Erasmus MC, Rotterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Years ago, we identified soluble (s) CD27 as a biomarker for T cell activation in body fluids, as part of my PhD study. (J Immunol. 1991 Jul 1;147(1):29-35.)
As we presume the neuropathology seen in MS is guided by T cells we were interested to be able to quantify the activity of such cells in a given patient.
Cerebrospinal fluid (CSF) is as close as we can get to the site of the disease process in MS, therefore we focus on biomarkers in this compartment.
We found clearly elevated levels of sCD27 in CSF of Multiple Sclerosis patients versus non-inflammatory controls.

In this study we investigated whether at the moment of first attack of suspected Multiple Sclerosis, quantification of CSF sCD27 can predict further progression in to a diagnosis of MS and whether sCD27 levels are correlated with later attack frequency. Indeed, we found that high sCD27 measured at this early stage predicts a more rapid diagnosis of Multiple Sclerosis and a more aggressive disease course.

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Mutliple Sclerosis: Ocrelizumab Lowers Rate of Disease Progression and Disability

MedicalResearch.com Interview with:

Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School part of UTHealth | The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030

Dr. Jerry Wolinsky,

Jerry S. Wolinsky, MD
Emeritus Professor in Neurology
McGovern Medical School
The University of Texas Health Science Center at Houston
Houston’s Health University
Department of Neurology
Houston, Texas 77030

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses.

However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval.

The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis.

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Multiple Sclerosis: Interim Report on the Safety and Efficacy of Long-Term Daclizumab Treatment for Up to Five Years

MedicalResearch.com Interview with
Ralph Kern, M.D.
Senior vice president, Worldwide Medical
Biogen

MedicalResearch.com: What is the background for this study?

Response: Previously reported clinical trials of daclizumab demonstrated significant efficacy across clinical and MRI measures, compared to placebo and interferon beta-1a 30 mcg intramuscular (IM) injection, and established the therapy’s safety profile for up to two to three years. These trials were the basis for approval by health authorities in the United States, European Union and Australia. Daclizumab is a once-monthly, self-administered, subcutaneous therapy for relapsing forms of MS (RMS).

At ECTRIMS we presented the first interim results from EXTEND, a long-term extension study. EXTEND is an ongoing multicenter, open-label study to evaluate the safety and efficacy of daclizumab treatment in more than 1,500 patients with RMS.

This interim ECTRIMS analysis includes up to five years of data from patients who were previously enrolled in DECIDE. DECIDE was a Phase 3 study evaluating the effects of daclizumab relative to interferon beta-1a IM. In the new analysis, patients who were treated with interferon beta-1a IM for two to three years in DECIDE switched to daclizumab when they enrolled in EXTEND, and were compared to daclizumab patients treated continuously in both DECIDE and EXTEND.

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Lack of Sunny Holidays in Northern Latitudes Linked to Low Vitamin D

MedicalResearch.com Interview with:
Ms Emily Weiss PhD student
Centre for Population Health Sciences
The University of Edinburgh

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Vitamin D deficiency, a marker of low ultraviolet (UV) exposure, is common in Scotland; both have been shown to work independently as risk factors for multiple sclerosis (MS). Orkney, situated to the north of mainland Scotland has a very high prevalence of MS. We therefore wanted to understand how vitamin D in Orkney compares to mainland Scotland’s vitamin D, and also what may be determining vitamin D levels in Orkney.
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Multiple Sclerosis: Generic Copaxone Demonstrates Equivalent Safety and Efficacy

Jeffrey Cohen MD Department of Neurology Cleveland ClinicMedicalResearch.com: Interview with:
Jeffrey A. Cohen, MD
Hazel Prior Hostetler Endowed Chair
Professor, Cleveland Clinic Lerner College of Medicine
Director, Mellen Center for MS Treatment and Research
Neurological Institute
Cleveland Clinic Cleveland, OH  44195

Medical Research: What are the main findings of the study?

Dr. Cohen: The primary objective of the GATE trial was to compare the efficacy and safety of generic glatiramer acetate to the approved form (Copaxone) in relapsing-remitting multiple sclerosis.  The study demonstrated equivalent efficacy of generic glatiramer acetate and Copaxone measured by gadolinium enhancing brain MRI lesions at months 7, 8, and 9 and a number of additional measures of MRI lesion activity.  The study also showed comparable safety (measured by adverse events) and injection site tolerability.

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Multiple Sclerosis: Sleep Disorders Both Common and Underdiagnosed

Steven D. Brass, M.D., M.P.H., M.B.A. PI and Lead Author on the study Director of Neurology Sleep Clinical Program Co-Medical Director of Sleep Medicine Laboratory Associate Clinical Professor in the Department of Neurology UC Davis Health System 4860 Y Street — Suite 3700 Sacramento, CA 95817 MedicalResearch.com Interview with:
Steven D. Brass, M.D., M.P.H., M.B.A.
PI and Lead Author on the study
Director of Neurology Sleep Clinical Program
Co-Medical Director of Sleep Medicine Laboratory
Associate Clinical Professor in the Department of Neurology
UC Davis Health System 4860 Y Street — Suite 3700
Sacramento, CA 95817

Medical Research: What was the primary finding of your study?

Dr. Brass : Among the 11,400 surveys mailed out to all members of the Northern California Chapter of the National Multiple Sclerosis Society, 2,810 (24.6%) were returned. Of these, 2,375 (84.5%) met the inclusion criteria. Among the completed surveys, 898 (37.8%) screened positive for obstructive sleep apnea, 746 (31.6%) for moderate to severe insomnia, and 866 (36.8%) for restless legs syndrome.  In contrast, only 4%, 11%, and 12% of the cohort reported being diagnosed by a health care provider with obstructive sleep apnea, insomnia, and restless legs syndrome, respectively. Excessive daytime sleepiness was noted in 30% of respondents based on the Epworth Sleepiness Scale. More than 60% of the respondents reported an abnormal level of fatigue based on the Fatigue Severity Scale.  There was also an increased risk between complaints of Fatigue based on screening positive for the Fatigue Severity Scale  and screening positive for Obstructive Sleep Apnea  (1.850, with a 95% p-value < 0.001).

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Multiple Sclerosis: Slower Walking Speed Associated With Decreased Quality of Life

Jeffrey Cohen MD Department of Neurology Cleveland ClinicMedicalResearch.com Interview with:
Jeffrey Cohen MD
Department of Neurology
Cleveland Clinic

Medical Research: What are the main findings of the study?

Dr. Cohen: This study assessed the relationship between walking speed, as measured by the Timed 25-foot Walk test, and patient-reported quality of life, as measured by the Physical Component Summary score of the 36-Item Short Form Health Survey (SF-36), in a pooled dataset from the AFFIRM, SENTINEL, and IMPACT multiple sclerosis Phase 3 trials.  It showed that slowed walking speed is associated with decreased quality of life.  It also showed that 20-25% slowing of walking speed is a clinically meaningful change.
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Multiple Sclerosis: Clinical Features and MRI Changes of Decision-Making Difficulties

Dr Nils Muhlert Wellcome Trust ISSF Research Fellow School of Psychology Cardiff UniversityMedicalResearch.com Interview with:
Dr Nils Muhlert
Wellcome Trust ISSF Research Fellow
School of Psychology
Cardiff University

Medical Research: What are the main findings of the study?

Dr. Muhlert: Decision making impairments are known to occur in people with multiple sclerosis (MS), and are important, given they can contribute to employment status, treatment compliance and function in everyday life. Studies by Kleeberg, Simioni and others have demonstrated that decision-making impairments can occur early in the course of multiple sclerosis and get worse as the disease progresses. Questions however remain over whether these impairments are linked to more general cognitive difficulties, differences between multiple sclerosis subtypes, and their relationship with MRI changes.

We assessed decision-making and examined MRI changes in a relatively large sample of people with multiple sclerosis (N = 105) and healthy controls (N = 43). All participants performed the Cambridge Gambling Task, which independently measures risk-taking, impulsivity, deliberation and risk adjustment, and underwent an MRI scan including T1-weighted and diffusion MRI sequences.

We demonstrate that people with multiple sclerosis experience difficulties with risk adjustment (gauging risk and adapting accordingly) and in the speed of making decisions but not in impulsivity. These problems were seen in those classified as having cognitive impairment and those not (i.e. cognitively unimpaired). We found that decision-making impairments were twice as common in people with relapsing-remitting and primary progressive MS than healthy controls, and almost four times as common in people with secondary progressive multiple sclerosis. In addition, decision making impairments in multiple sclerosis were linked to MRI changes in regions previously linked to decision-making in other conditions, including fronto-striatal and hippocampal regions. These findings offer insight into the precise decision-making difficulties experienced by people with multiple sclerosis, the relative prevalences in different subtypes of the disease and the pathological processes that may underlie them.

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Multiple Sclerosis: Monoclonal Antibody Tysabri Reduces Brain Inflammation

Jeppe Romme Christensen  MD PhD From the Danish Multiple Sclerosis Center Copenhagen University Hospital Hvidovre, Denmark.MedicalResearch.com Interview with:
Jeppe Romme Christensen  MD PhD
From the Danish Multiple Sclerosis Center
Copenhagen University Hospital Hvidovre, Denmark.

MedicalResearch.com: What are the main findings of the study?

Dr. Christensen: This study demonstrates that progressive multiple sclerosis (MS) patients have reduced inflammation and tissue damage in the brain after treatment with natalizumab. These findings highlight that progressive MS is an inflammatory disease and furthermore that peripheral circulating immune cells contribute to brain inflammation and tissue damage in progressive MS.

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Incidence of multiple sclerosis in multiple racial and ethnic groups

MedicalResearch.com eInterview with Annette Langer-Gould, MD, PhD

From the Department of Research and Evaluation Kaiser Permanente,
Southern California, Pasadena; and Neurology Department
Kaiser Permanente, Southern California Los Angeles Medical Center, CA.

MedicalResearch.com: What are the main findings of the study?

Dr. Langer-Gould: The main findings of the study were that multiple sclerosis is more common in black women than in white women, which run contrary to the widely accepted belief that blacks are less susceptible to MS. In particular, we found that black patients had a 47 percent higher risk of MS than white patients, while Hispanic and Asian patients had a 50 percent and 80 percent lower risk compared to white patients, respectively. We also found that 70 percent of MS cases occurred in females, but this preponderance of females diagnosed was more pronounced among black patients than white patients. In addition, black women had a higher incidence of MS than white patients of both genders, while black men had a similar risk of being diagnosed with MS compared to white men. The lower risk among Hispanic and Asian patients was true for both sexes.
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New Multiple Sclerosis Gene Associations Discovered

An international team of scientists has identified 29 new genetic variants linked to multiple sclerosis, providing key insights into the biology of an important and very debilitating neurological disease.

Multiple sclerosis (MS), one of the most common neurological conditions among young adults, affects around 2.5 million individuals worldwide. It is a chronic disease that attacks the central nervous system (CNS), which includes the brain, spinal cord and optic nerves, and can cause severe symptoms such as paralysis or loss of vision.

Vanderbilt University Medical Center’s Center for Human Genetics Research (CHGR) played an important role in the research published today in the journal Nature, which represents the largest MS genetics study ever undertaken and effectively doubles the number of genes known to be associated with the disease.

“We now know just how complex multiple sclerosis is,” said Jonathan Haines, Ph.D., director of the CHGR and one of the principal researchers in this effort. “These new genes give us many new clues as to what is happening in MS and will guide our research efforts for years to come.”

Researchers studied the DNA from 9,772 individuals with multiple sclerosis and 17,376 unrelated healthy controls. They were able to confirm 23 previously known genetic associations and identified a further 29 new genetic variants (and an additional five that are strongly suspected) conferring susceptibility to the disease.

Many genes implicated in the study are relevant to the immune system, shedding light onto the immunological pathways that underlie the development of multiple sclerosis.

One-third of the genes identified in the study have previously been implicated in playing a role in other autoimmune diseases such as Crohn’s Disease and Type 1 diabetes, Haines said.

Previous studies have also suggested a link between vitamin D deficiency and an increased risk of multiple sclerosis; researchers in this study identified two genes involved in the metabolism of vitamin D, providing additional insight into a possible link between genetic and environmental risk factors.

The international team led by the Universities of Cambridge and Oxford, and funded by the Wellcome Trust, includes contributions from nearly 250 researchers as members of the International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium.