No abstract

Objective: To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis. Methods: A total of 943 patients with primary progressive multiple sclerosis were randomized to GA or placebo (PBO) in this 3-year, double-blind trial. The primary end point was an intention-to-treat analysis of time to 1-(entry expanded disability status scale, 3.0 -5.0) or 0.5-point expanded disability status scale change (entry expanded disability status scale, 5.5-6.5) sustained for 3 months. The trial was stopped after an interim analysis by an independent data safety monitoring board indicated no discernible treatment effect on the primary outcome. Intention-to-treat analyses of disability and magnetic resonance imaging end points were performed. Results: There was a nonsignificant delay in time to sustained accumulated disability in GA-versus PBO-treated patients (hazard ratio, 0.87 [95% confidence interval, 0.71-1.07]; p ϭ 0.1753), with significant decreases in enhancing lesions in year 1 and smaller increases in T2 lesion volumes in years 2 and 3 versus PBO. Post hoc analysis showed that survival curves for GA-treated male patients diverged early from PBO-treated male subjects (hazard ratio, 0.71 [95% confidence interval, 0.53-0.95]; p ϭ 0.0193). Interpretation:The trial failed to demonstrate a treatment effect of GA on primary progressive multiple sclerosis. Both the unanticipated low event rate and premature discontinuation of study medication decreased the power to detect a treatment effect. Post hoc analysis suggests GA may have slowed clinical progression in male patients who showed more rapid progression when untreated.

Autoimmune myasthenia gravis (MG) is associated with antibodies directed against the nicotinic acetylcholine receptor (AChR) in 85% of patients. Other postsynaptic neuromuscular junction antigens are implicated, e.g., muscle-specific receptor tyrosine kinase (MuSK), in a number of the remaining 15% of patients, so-called seronegative MG. The autoimmune attack generally leads to decreased concentrations of the AChR and damage to the structure of the endplate itself. This information has guided the empiric treatment of patients with MG and has suggested new treatment strategies. Whereas the outcome of patients with MG has improved because of more effective symptomatic treatment, including advances in critical care medicine and the use of cholinesterase inhibitors, the greatest advances have come from therapies that directly reduce the autoimmune attack or modify its effects on the AChR and the surrounding endplate. Immune-directed treatment of patients with MG, which is guided by this information and by data from the management of other autoimmune disease, is aimed at inducing an immunologic remission and then maintaining that remission. Remission induction is usually accomplished through the use of high-dose corticosteroids, frequently in conjunction with IV immunoglobulin or plasmapheresis. Maintenance of the remission is usually accomplished by slow tapering of the corticosteroids along with the use of "steroid-sparing" agents, which include azathioprine, thymectomy, and possibly mycophenolate. Therapy usually begins with cholinesterase inhibitors. If necessary, immune-directed treatment is added, beginning with either thymectomy or high-dose corticosteroids. The short-term therapies, i.e., IV immunoglobulin or plasmapheresis, may be effective in the early stages of treatment or later during an exacerbation. Steroid-sparing medications are usually added to facilitate the tapering phase.

Inebilizumab had an acceptable safety profile in relapsing MS patients and showed a trend in reductions in new/newly enlarging and gadolinium-enhancing lesions.