scholarly journals Disease-modifying treatments for progressive multiple sclerosis

2013 ◽  
Vol 19 (11) ◽  
pp. 1428-1436 ◽  
Author(s):  
Giancarlo Comi
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Laboratory Science ◽  
New Concepts ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Major Progress

The last 20 years have seen major progress in the treatment of relapsing–remitting multiple sclerosis (RRMS) using a variety of drugs targeting immune dysfunction. In contrast, all clinical trials of such agents in primary progressive multiple sclerosis (PPMS) have failed and there is limited evidence of their efficacy in secondary progressive disease. Evolving concepts of the complex interplay between inflammatory and neurodegenerative processes across the course of multiple sclerosis (MS) may explain this discrepancy. This paper will provide an up-to-date overview of the rationale and results of the published clinical trials that have sought to alter the trajectory of both primary and secondary MS, considering studies involving drugs with a primary immune target and also those aiming for neuroprotection. Future areas of study will be discussed, building on these results combined with the experience of treating RRMS and new concepts emerging from laboratory science and animal models.

scholarly journals Ocrelizumab-induced alopecia areata—A series of five patients from Ontario, Canada: A case report

2020 ◽  
Vol 8 ◽  
pp. 2050313X2091961
Author(s):  
Laura D Chin ◽  
Mohn’d AbuHilal
Keyword(s):  
Multiple Sclerosis ◽  
Alopecia Areata ◽  
Conventional Treatment ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Cd20 Antigen ◽  
Humanized Monoclonal Antibody ◽  
Relapsing Remitting ◽  
Topical Minoxidil ◽  
Relapsing Remitting Multiple Sclerosis

Background: Ocrelizumab is a humanized monoclonal antibody that targets the CD20 antigen found on B-cells. It is indicated in the treatment of both relapsing–remitting multiple sclerosis and primary progressive multiple sclerosis. Objective: The aim of this study is to report and describe the characteristics of alopecia areata following treatment with ocrelizumab for multiple sclerosis. Results: Five patients were reported, two female and three male. Four of the five patients had alopecia areata of the scalp, one of the five having alopecia to the beard area. All patients responded well to conventional treatment with topical and intralesional corticosteroids and topical minoxidil foam. Ocrelizumab can be associated with the development of alopecia areata. Initiation of proper treatment may lead to quick improvement or resolution of this potentially reversible adverse effect.

scholarly journals Use and cost of disease-modifying therapies by Sonya Slifka Study participants: has anything really changed since 2000 and 2009?

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731882088 ◽  
Author(s):  
Sarah L Minden ◽  
R Philip Kinkel ◽  
Helene T Machado ◽  
Jonathan S Levin ◽  
Meredith B Rosenthal ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family Income ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies benefit individuals with relapsing forms of multiple sclerosis, but their utility remains unclear for those without relapses. Objective To determine disease-modifying therapy use and costs in 2009, compare use in 2009 and 2000, and examine compliance with evidence-based guidelines. Methods We determined the extent and characteristics of disease-modifying therapy use by participants in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka) in 2000 ( n=2156) and 2009 ( n=2361) and estimated out-of-pocket and total (payer) costs for 2009. Two multivariable logistic regressions predicted disease-modifying therapy use. Results Disease-modifying therapy use increased from 55.3% in 2000 to 61.5% in 2009. In 2009, disease-modifying therapy use was reported by 76.5% of participants with relapsing-remitting multiple sclerosis, 73.2% with progressive-relapsing multiple sclerosis, 62.5% with secondary progressive multiple sclerosis, and 41.8% with primary progressive multiple sclerosis. Use was significantly associated with relapsing-remitting multiple sclerosis, shorter duration of illness, one to two relapses per year, non-ambulatory symptoms, using a cane, younger age, higher family income, and having health insurance. Average annual costs in 2009 were US$939–3101 for patients and US$16,302–18,928 for payers. Conclusion Use rates were highest for individuals with relapsing-remitting multiple sclerosis, but substantial for those with progressive courses although clinical trials have not demonstrated significant benefits for them.

scholarly journals Risk factors for leaving employment due to multiple sclerosis and changes in risk over the past decades: Using competing risk survival analysis

2020 ◽  
pp. 135245852095416
Author(s):  
Jing Chen ◽  
Bruce Taylor ◽  
Leigh Blizzard ◽  
Steve Simpson-Yap ◽  
Andrew J Palmer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Survival Analysis ◽  
Progressive Multiple Sclerosis ◽  
Education Level ◽  
Competing Risk ◽  
Primary Progressive Multiple Sclerosis ◽  
Lower Education Level ◽  
Relapsing Remitting ◽  
Lower Education ◽  
Relapsing Remitting Multiple Sclerosis

Background: No studies have assessed changes in employment survival in multiple sclerosis (MS) populations over recent decades, including the introduction of disease-modifying therapies (DMTs). Objectives: To evaluate factors associated with leaving employment due to MS; to assess whether the risk of leaving employment has changed over recent decades in Australia, stratified by MS phenotype. Methods: We included 1240 participants who were working before MS diagnosis. Information on employment status, reasons for leaving employment and year of leaving were collected. Data were analysed using competing risk survival analysis. Results: Males, progressive MS, lower education level and older age at diagnosis were associated with a higher sub-distribution hazard of leaving employment. Compared to the period before 2010, the sub-distribution hazard during 2010–2016 for relapsing-remitting multiple sclerosis (RRMS) was reduced by 43% (sub-distribution hazard ratio (sHR) 0.67, 95% confidence interval (CI): 0.50 to 0.90), while no significant reduction was seen for primary-progressive multiple sclerosis (PPMS) (sHR 1.25, 95% CI: 0.72 to 2.16) or secondary-progressive multiple sclerosis (SPMS) (sHR 1.37, 95% CI: 0.84 to 2.25). Conclusion: Males, people with progressive MS and those of lower education level were at higher risk of leaving employment. The differential changed risk of leaving employment between people with different MS phenotype after 2010 coincides with the increased usage of high-efficacy DMTs for RRMS.

ECTRIMS/ACTRIMS 2017: Closing in on neurorepair in progressive multiple sclerosis

2018 ◽  
Vol 24 (6) ◽  
pp. 696-700 ◽  
Author(s):  
David Kremer ◽  
Patrick Küry ◽  
Hans-Peter Hartung
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Progressive Multiple Sclerosis ◽  
Treatment Goal ◽  
European Committee ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Tool Set ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Stimulation Of

Background: While there is now a multitude of potent medications for relapsing-remitting multiple sclerosis (RRMS), effective therapies targeting neurodegeneration in progressive multiple sclerosis types are still lacking. Stimulation of neurorepair in this disease remains a pathogenetically defined treatment goal. However, therapeutic progress is slowed by the still inadequate tool set to capture “regeneration/repair” in MS and to define appropriate outcomes in clinical trials. Objectives: In this review, we discuss studies investigating promising regenerative agents for progressive MS which were recently presented during the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)/Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017 meeting in Paris.

Dengue fever in a multiple sclerosis patient taking Ocrelizumab

2021 ◽  
pp. 135245852110302
Author(s):  
Tommaso Guerra ◽  
Luca Bollo ◽  
Maria Trojano ◽  
Pietro Iaffaldano
Keyword(s):  
Infectious Disease ◽  
Multiple Sclerosis ◽  
Dengue Fever ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Cd20 Antigen ◽  
Humanized Monoclonal Antibody ◽  
Relapsing Remitting ◽  
Favorable Clinical Outcome ◽  
Relapsing Remitting Multiple Sclerosis

Dengue fever (DF) is an endemic infectious disease in tropical and subtropical regions. Ocrelizumab is a humanized monoclonal antibody that targets the CD20 antigen on B cells, which is approved for the treatment of both relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS). We describe the favorable clinical outcome of DF in an RRMS patient treated with Ocrelizumab, who neither presented hemorrhagic or systemic shock symptoms nor reported neurological worsening.

Primary progressive multiple sclerosis: a distinct syndrome?

1996 ◽  
Vol 2 (3) ◽  
pp. 137-141 ◽  
Author(s):  
GV McDonnell ◽  
SA Hawkins
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Progressive Decline ◽  
Primary Progressive ◽  
Therapeutic Trials ◽  
Relapsing Remitting ◽  
Progressive Course

Multiple sclerosis (MS) has long been recognised to have both a relapsing-remitting and progressive course. More recently patients with progressive disease have been further sub-divided into those with a progressive course from onset (primary progressive MS) and those with progressive decline following an initially relapsing-remitting period (secondary progressive MS). Diversity in MS may not however be restricted to clinical course. There is growing evidence that the subgroups of MS also differ with respect to clinical features, epidemiology, pathogenesis, genetics and neuroimaging appearances. In this review we outline the criteria variously applied in the classification of MS patients, addressing the need for a dear nomenclature. We evaluate the proposition that primary progressive MS has a prof ile distinct from other MS categories, contrasting the separate differential diagnoses and examining the implications for future therapeutic trials.

scholarly journals In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis

2017 ◽  
Vol 24 (8) ◽  
pp. 1029-1038 ◽  
Author(s):  
In-Young Choi ◽  
Phil Lee ◽  
Peter Adany ◽  
Abbey J Hughes ◽  
Scott Belliston ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Brain Atrophy ◽  
Disease Status ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: The oxidative stress hypothesis links neurodegeneration in the later, progressive stages of multiple sclerosis (MS) to the loss of a major brain antioxidant, glutathione (GSH). Objective: We measured GSH concentrations among major MS subtypes and examined the relationships with other indices of disease status including physical disability and magnetic resonance imaging (MRI) measures. Methods: GSH mapping was performed on the fronto-parietal region of patients with relapsing-remitting multiple sclerosis (RRMS, n = 21), primary progressive multiple sclerosis (PPMS, n = 20), secondary progressive multiple sclerosis (SPMS, n = 20), and controls ( n = 28) using GSH chemical shift imaging. Between-group comparisons were performed on all variables (GSH, T2-lesion, atrophy, Expanded Disability Status Scale (EDSS)). Results: Patients with MS had substantially lower GSH concentrations than controls, and GSH was lower in progressive MS (PPMS and SPMS) compared with RRMS. GSH concentrations were not significantly different between PPMS and SPMS, or between RRMS and controls. Brain atrophy was significant in both RRMS and progressive MS compared with controls. Conclusion: Markedly lower GSH in progressive MS than RRMS indicates more prominent involvement of oxidative stress in the progressive stage of MS than the inflammatory stage. The association between GSH and brain atrophy suggests the important role of oxidative stress contributing to neurodegeneration in progressive MS, as suggested in other neurodegenerative diseases.

Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and is upregulated in reactive astrocytes

2016 ◽  
Vol 23 (13) ◽  
pp. 1707-1715 ◽  
Author(s):  
Massimiliano Cristofanilli ◽  
Daniel Gratch ◽  
Benjamin Pagano ◽  
Kelsey McDermott ◽  
Jessie Huang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter Lesions ◽  
Progressive Multiple Sclerosis ◽  
Reactive Astrocytes ◽  
Primary Progressive Multiple Sclerosis ◽  
Autoimmune Encephalomyelitis ◽  
Cultured Astrocytes ◽  
Relapsing Remitting ◽  
Antibody Levels ◽  
Relapsing Remitting Multiple Sclerosis

Background: Transglutaminase-6 (TGM6), a member of the transglutaminase enzyme family, is found predominantly in central nervous system (CNS) neurons under physiological conditions. It has been proposed as an autoimmune target in cerebral palsy, gluten-sensitive cerebellar ataxia, and schizophrenia. Objective: To investigate TGM6 involvement in multiple sclerosis (MS). Methods: Antibody levels against TGM6 (TGM6-IgG) were measured in the cerebrospinal fluid (CSF) of 62 primary progressive multiple sclerosis (PPMS), 85 secondary progressive multiple sclerosis (SPMS), and 50 relapsing-remitting multiple sclerosis (RRMS) patients and 51 controls. TGM6 protein expression was analyzed in MS brain autopsy, murine experimental autoimmune encephalomyelitis (EAE), and cultured astrocytes. Results: CSF levels of TGM6-IgG were significantly higher in PPMS and SPMS compared to RRMS and controls. Notably, patients with clinically active disease had the highest TGM6-IgG levels. Additionally, brain pathology revealed strong TGM6 expression by reactive astrocytes within MS plaques. In EAE, TGM6 expression in the spinal cord correlated with disease course and localized in reactive astrocytes infiltrating white matter lesions. Finally, knocking down TGM6 expression in cultured reactive astrocytes reduced their glial fibrillary acidic protein (GFAP) expression. Conclusion: TGM6-IgG may be a candidate CSF biomarker to predict and monitor disease activity in progressive MS patients. Furthermore, TGM6 expression by reactive astrocytes within both human and mouse lesions suggests its involvement in the mechanisms of glial scar formation.

A contemporary profile of primary progressive multiple sclerosis participants from the NARCOMS Registry

2017 ◽  
Vol 24 (7) ◽  
pp. 951-962 ◽  
Author(s):  
Amber Salter ◽  
Nina P Thomas ◽  
Tuula Tyry ◽  
Gary R Cutter ◽  
Ruth Ann Marrie
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Population Based ◽  
Primary Progressive Multiple Sclerosis ◽  
Research Committee ◽  
Primary Progressive ◽  
The North ◽  
Relapsing Remitting ◽  
Health Related ◽  
Relapsing Remitting Multiple Sclerosis

Background: Primary progressive multiple sclerosis (PPMS) represents 10%–15% of all multiple sclerosis (MS) diagnoses. Information regarding socio-demographic and clinical characteristics of persons with PPMS is limited. Objective: To characterize persons with PPMS in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Methods: We compared demographic and health-related characteristics of NARCOMS Registry participants reporting PPMS in the spring 2015 update survey with those reporting relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), with characteristics of published PPMS cohorts. Results: Of 8004 responders, 6774 self-reported a clinical course of PPMS, SPMS, or RRMS. The PPMS cohort ( n = 632, 9.3%) reported a mean (standard deviation (SD)) age of 64.3 (8.9) years; 62.7% were female; the SPMS and RRMS cohorts were younger and had a higher proportion of females. The NARCOMS PPMS cohort differed in age, time from onset and diagnosis, and proportion of females compared to population-based and clinical trial cohorts. Median (25%, 75%) number of comorbidities was 2 (1, 2) for each cohort with vascular comorbidities being most frequently reported. Conclusion: The NARCOMS population provides a different perspective on persons with PPMS than clinical trials. A better understanding of the characteristics of persons with PPMS may help address unmet needs in this population.

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