Multiple sclerosis : clinical and laboratory research
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Review Meta Analysis
Indirect comparisons of treatment effects: Network meta-analyses.
Many therapeutic options are now available for patients with multiple sclerosis. While the efficacy of each drug has been assessed against placebo or, more recently, against interferon, no direct comparisons of these new therapies have been conducted in randomized clinical trials. Therefore, indirect treatment comparisons are needed to inform clinical decisions. In this brief report, some basic concepts about network meta-analyses that are the formal methods used to run multiple indirect treatment comparisons are reviewed when applied in the context of multiple sclerosis studies.
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Meta Analysis
Atrophy and structural variability of the upper cervical cord in early multiple sclerosis.
Despite agreement about spinal cord atrophy in progressive forms of multiple sclerosis (MS), data on clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) are conflicting. ⋯ In MS, cervical cord atrophy already occurs in CIS. In early stages, structural variability may be a more meaningful marker of spinal cord pathology than atrophy.
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Review Meta Analysis
Alemtuzumab: a new therapy for active relapsing-remitting multiple sclerosis.
Alemtuzumab is a humanized monoclonal antibody directed against CD52 to deplete circulating T and B lymphocytes; lymphocyte depletion is followed by a distinctive pattern of T- and B-cell repopulation, changing the balance of the immune system. This review reports the efficacy and safety findings of the phase 2 CAMMS223 trial and the phase 3 CARE-MS I and II trials investigating alemtuzumab for the treatment of active relapsing-remitting MS. Alemtuzumab, administered intravenously, was shown to improve relapse rate versus subcutaneous interferon beta-1a in patients who were treatment-naive (CAMMS223 and CARE-MS I) or had relapsed on prior therapy (CARE-MS II), and to reduce sustained accumulation of disability (CAMMS223 and CARE-MS II). ⋯ A safety monitoring program allowed for early detection and management of autoimmune events. Recommendations for the monitoring of adverse events are made. Alemtuzumab's mechanism of action, pharmacodynamics and opportunities for future research are discussed.
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Meta Analysis
Magnetic resonance imaging as surrogate for clinical endpoints in multiple sclerosis: data on novel oral drugs.
Recent studies have provided evidence for using magnetic resonance imaging (MRI) active lesions as surrogate for relapses and disability progression in multiple sclerosis (MS). However, the validity of MRI metrics as surrogate endpoints in MS is controversial. ⋯ The 92% of observed effects of oral drugs on clinical outcomes resulted close to those predicted by MRI active lesions. This further validates MRI surrogacy in MS, with important implications for future trials planning.
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To estimate the incidence and severity of nocebo responses in trials of symptomatic treatments (STs) and disease-modifying treatments (DMTs) for multiple sclerosis (MS). ⋯ Nocebo responses in MS trials are substantial and appear to have increased significantly in recent years with important implications for both trial design and clinical practice. Furthermore, nocebo responses exhibit an association with medication and trial-related factors.