Personalized treatment is ideal for multiple sclerosis (MS) owing to the heterogeneity of clinical features, but current knowledge gaps, including validation of biomarkers and treatment algorithms, ...limit practical implementation. The contemporary approach to personalized MS therapy depends on evidence-based prognostication, an initial treatment choice and evaluation of early treatment responses to identify the need to switch therapy. Prognostication is directed by baseline clinical, environmental and demographic factors, MRI measures and biomarkers that correlate with long-term disability measures. The initial treatment choice should be a shared decision between the patient and physician. In addition to prognosis, this choice must account for patient-related factors, including comorbidities, pregnancy planning, preferences of the patients and their comfort with risk, and drug-related factors, including safety, cost and implications for treatment sequencing. Treatment response has traditionally been assessed on the basis of relapse rate, MRI lesions and disability progression. Larger longitudinal data sets have enabled development of composite outcome measures and more stringent standards for disease control. Biomarkers, including neurofilament light chain, have potential as early surrogate markers of prognosis and treatment response but require further validation. Overall, attainment of personalized treatment for MS is complex but will be refined as new data become available.
Multiple sclerosis is a chronic, predominantly immune-mediated disease of the central nervous system, and one of the most common causes of neurological disability in young adults globally. This ...review will discuss the epidemiology, diagnosis, disease course, and prognosis of multiple sclerosis and will focus on recent evidence and advances in these aspects of the disease.
Multiple sclerosis is increasing in incidence and prevalence globally, even in traditionally low-prevalence regions of the world. Recent revisions have been proposed to the existing multiple sclerosis diagnostic criteria, which will facilitate earlier diagnosis and treatment in appropriate patients. Classifying multiple sclerosis into distinct disease phenotypes can be challenging, and recent refinements have been proposed to clarify existing definitions. The prognosis of multiple sclerosis varies substantially across individual patients, and a combination of clinical, imaging, and laboratory markers can be useful in predicting clinical course and optimizing treatment in individual patients.
A number of recent advances have been made in the clinical diagnosis and prognostication of multiple sclerosis patients. Future research will enable the development of more accurate biomarkers of disease categorization and prognosis, which will enable timely personalized treatment in individual multiple sclerosis patients.
Body fluid biomarkers in multiple sclerosis Comabella, Manuel, Dr; Montalban, Xavier, Prof
Lancet neurology,
2014, January 2014, 2014-Jan, 2014-01-00, 20140101, Letnik:
13, Številka:
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Journal Article
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Summary Biomarkers can be thought of as multifaceted indicators of healthy status or of pathological disorders. The study of multiple sclerosis can benefit from the use of biomarkers because of the ...disease's inherent heterogeneity. Biomarkers in multiple sclerosis might assist with diagnosis, prediction of disease course, or identification of response outcome to treatments. Despite the need for biomarkers and extensive research to identify them, validation and clinical application of biomarkers is still an unmet need in multiple sclerosis, and large gaps remain between exploratory biomarkers proposed in many studies, validated biomarkers, and biomarkers that are integrated into routine clinical practice.
In a randomized trial, patients who received evobrutinib, an inhibitor of Bruton’s tyrosine kinase, at 75 mg daily had significantly fewer enhancing lesions on MRI during weeks 12 through 24 than ...those who received placebo. However, there was no significant between-group difference for either a lower or a higher dose of evobrutinib, or in the annualized relapse rate or disability progression at any dose.
B cells play a central role in the pathogenesis of multiple sclerosis (MS): they are involved in the activation of pro-inflammatory T cells, secretion of pro-inflammatory cytokines and production of ...autoantibodies directed against myelin. Hence, the use of B cell-depleting monoclonal antibodies as therapy for autoimmune diseases, including MS, has increased in recent years. Previous results with rituximab, the first therapeutic B cell-depleting chimeric monoclonal antibody that showed efficacy in MS clinical trials, encouraged researchers to evaluate the efficacy of a humanized anti-CD20 antibody, ocrelizumab, in MS. A large phase II clinical trial in patients with relapsing-remitting MS (RRMS) designed to explore the effects of two doses of ocrelizumab (600 mg and 2000 mg) compared with placebo showed a pronounced effect on radiological and relapse-related outcomes. These results were confirmed in two phase III trials (OPERA I and II) that compared the efficacies of ocrelizumab with interferon beta-1a in patients with relapsing MS, and showed decreased annualized relapse rates (46% in OPERA I and 47% in OPERA II), as well as fewer numbers of gadolinium-enhanced lesions on magnetic resonance imaging (MRI) scans (94% in OPERA I and 95% in OPERA II). Notably, ocrelizumab is the first drug to lower rates of clinical and MRI-evidenced progression in patients with primary progressive MS (PPMS). The phase III trial (ORATORIO) in patients with PPMS met its primary efficacy endpoint: the percentage of patients with 12-week confirmed disability progression was significantly lower in the active treatment group (32.9%) than in patients receiving placebo (39.3%). In March 2017, this evidence led the US Food and Drug Administration to approve the licence for ocrelizumab (Ocrevus®) as a treatment for MS, as the first treatment approved for PPMS and as the first monoclonal antibody for secondary progressive MS.
Summary In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in ...space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.
Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most ...useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions - the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and spinal cord atrophy with MRI. MRI measurements of atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and spinal cord atrophy in clinical practice in the management of MS, considering the role of atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research.
In two trials involving patients with relapsing multiple sclerosis, the anti-CD20+ monoclonal antibody ocrelizumab was associated with lower annualized relapse rates, lower risk of disability ...progression, and better MRI features than interferon beta-1a.
Despite the availability of several disease-modifying treatments for relapsing forms of multiple sclerosis, patients often continue to have clinical and subclinical disease activity, and neurologic disability continues to accrue. Thus, there is a need for more effective treatments with acceptable safety profiles.
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B cells are thought to influence the underlying pathogenesis of multiple sclerosis by means of antigen presentation,
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autoantibody production,
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cytokine regulation,
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and the formation of ectopic lymphoid aggregates in the meninges, which possibly contribute to cortical demyelination and neurodegeneration.
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Ocrelizumab is a humanized monoclonal antibody that selectively targets CD20, a cell-surface antigen that is expressed . . .
Ofatumumab versus Teriflunomide in Multiple Sclerosis Hauser, Stephen L; Bar-Or, Amit; Cohen, Jeffrey A ...
New England journal of medicine/The New England journal of medicine,
08/2020, Letnik:
383, Številka:
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In two identical trials involving a total of 1882 patients with multiple sclerosis, the human anti-CD20 monoclonal antibody ofatumumab was associated with a lower annualized relapse rate than the ...pyrimidine-synthesis inhibitor teriflunomide, as well as fewer lesions on MRI.
Patients with primary progressive MS who received the anti-CD20+ humanized antibody ocrelizumab were less likely to have clinical deterioration that was sustained for 12 weeks than those who received ...placebo. The drug was associated with decreased lesion activity on MRI.
Primary progressive multiple sclerosis accounts for 10 to 15% of the overall population with multiple sclerosis.
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The course of this disease differs from those of relapsing–remitting and secondary progressive forms of multiple sclerosis in that progression consists mainly of gradual worsening of neurologic disability from symptom onset, although relapses may occur.
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Phase 3 trials in primary progressive multiple sclerosis have been unsuccessful,
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and no disease-modifying treatments have been approved.
B cells contribute to the pathogenesis of multiple sclerosis, including the primary progressive form.
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Although the mechanisms of tissue injury in multiple sclerosis are uncertain, B cells may influence pathogenesis . . .
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