We studied copolymer 1 (Copaxone) in a multicenter (11-university) phase III trial of patients with relapsing-remitting multiple sclerosis (MS). Two hundred fifty-one patients were randomized to receive copolymer 1 (n = 125) or placebo (n = 126) at a dosage of 20 mg by daily subcutaneous injection for 2 years. The primary end point was a difference in the MS relapse rate. The final 2-year relapse rate was 1.19 +/- 0.13 for patients receiving copolymer 1 and 1.68 +/- 0.13 for those receiving placebo, a 29% reduction in favor of copolymer 1 (p = 0.007) (annualized rates = 0.59 for copolymer 1 and 0.84 for placebo). Trends in the proportion of relapse-free patients and median time to first relapse favored copolymer 1. Disability was measured by the Expanded Disability Status Scale (EDSS), using a two-neurologist (examining and treating) protocol. When the proportion of patients who improved, were unchanged, or worsened by > or = 1 EDSS step from baseline to conclusion (2 years) was evaluated, significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened (p = 0.037). Patient withdrawals were 19 (15.2%) from the copolymer 1 group and 17 (13.5%) from the placebo group at approximately the same intervals. The treatment was well tolerated. The most common adverse experience was an injection-site reaction. Rarely, a transient self-limited systemic reaction followed the injection in 15.2% of those receiving copolymer 1 and 3.2% of those receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Although time to CDP between groups was not significant, overall subgroup analyses suggest selective B-cell depletion may affect disease progression in younger patients, particularly those with inflammatory lesions.

Background and objectivesDiagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis.MethodsUsing available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases.ResultsWe present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system.ConclusionsDifferential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.

IFNbeta-1a 44 micro g subcutaneously tiw was more effective than IFNbeta-1a 30 micro g IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.