Background: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis.
Methods: In this randomised, double-blind trial, undertaken in 80 sites in 16 countries, 481 patients presenting with a clinically isolated syndrome with unifocal manifestation, and two or more T2-weighted brain lesions measuring 6 mm or more, were randomly assigned to receive either subcutaneous glatiramer acetate 20 mg per day (n=243) or placebo (n=238) for up to 36 months, unless they converted to clinically definite multiple sclerosis. The randomisation scheme used SAS-based blocks stratified by centre, and patients and all personnel were masked to treatment assignment. The primary endpoint was time to clinically definite multiple sclerosis, based on a second clinical attack. Analysis was by intention to treat. A preplanned interim analysis was done for data accumulated from 81% of the 3-year study exposure. This study was registered with ClinicalTrials.gov, number NCT00666224.
Findings: All randomly assigned participants were analysed for the primary outcome. Glatiramer acetate reduced the risk of developing clinically definite multiple sclerosis by 45% compared with placebo (hazard ratio 0.55, 95% CI 0.40-0.77; p=0.0005). The time for 25% of patients to convert to clinically definite disease was prolonged by 115%, from 336 days for placebo to 722 days for glatiramer acetate. The most common adverse events in the glatiramer acetate group were injection-site reactions (135 [56%] glatiramer acetate vs 56 [24%] placebo) and immediate post-injection reactions (47 [19%] vs 12 [5%]).
Interpretation: Early treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI.
Funding: Teva Pharmaceutical Industries, Israel.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/S0140-6736(09)61259-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Intralesional injection of CpG ODNs complexed with glatiramer acetate mitigates systemic cytokine toxicities and synergistically advances checkpoint blockade efficacy.
Drug Deliv Transl Res
January 2025
Kinimmune, Inc. St. Louis, 63141, Missouri, USA.
PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.
View Article and Find Full Text PDFExploring the Pathophysiology, Diagnosis, and Treatment Options of Multiple Sclerosis.
J Integr Neurosci
January 2025
Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy.
The complicated neurological syndrome known as multiple sclerosis (MS) is typified by demyelination, inflammation, and neurodegeneration in the central nervous system (CNS). Managing this crippling illness requires an understanding of the complex interactions between neurophysiological systems, diagnostic techniques, and therapeutic methods. A complex series of processes, including immunological dysregulation, inflammation, and neurodegeneration, are involved in the pathogenesis of MS.
View Article and Find Full Text PDFEffect of Different Treatments on Retinal Thickness Changes in Patients With Multiple Sclerosis: A Review.
CNS Neurosci Ther
January 2025
Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran.
Background: Multiple sclerosis (MS) is an autoimmune disorder affecting the central nervous system, with varying clinical manifestations such as optic neuritis, sensory disturbances, and brainstem syndromes. Disease progression is monitored through methods like MRI scans, disability scales, and optical coherence tomography (OCT), which can detect retinal thinning, even in the absence of optic neuritis. MS progression involves neurodegeneration, particularly trans-synaptic degeneration, which extends beyond the initial injury site.
View Article and Find Full Text PDFAntimicrobial peptide glatiramer acetate targets Pseudomonas aeruginosa lipopolysaccharides to breach membranes without altering lipopolysaccharide modification.
NPJ Antimicrob Resist
February 2024
National Heart and Lung Institute, Imperial College London, London, UK.
Antimicrobial peptides (AMPs) are key components of innate immunity across all domains of life. Natural and synthetic AMPs are receiving renewed attention in efforts to combat the antimicrobial resistance (AMR) crisis and the loss of antibiotic efficacy. The gram-negative pathogen Pseudomonas aeruginosa is one of the most concerning infecting bacteria in AMR, particularly in people with cystic fibrosis (CF) where respiratory infections are difficult to eradicate and associated with increased morbidity and mortality.
View Article and Find Full Text PDFCryptococcal-associated immune reconstitution inflammatory syndrome (C-IRIS) is a clinical worsening or new presentation of cryptococcal disease following the initiation of antiretroviral therapy. C-IRIS is primarily driven by an influx of pathological CD4 T cells, which triggers a hyperinflammatory response. The murine model of C-IRIS is a way to study the disease in mice and understand how the immune system triggers life-threatening outcomes in patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!