ECTRIMS 2023
The annual ECTRIMS meeting was held October 11-13 in Milan, Italy. As usual, a lot of new information was presented on many topics. There was not much new on treatment for MS. The two presentations that I found particularly noteworthy were a report of phase II trials of fenebrutinib and frexalimab. Phase II trials are the second stage of testing in humans, and usually include about 200 subjects treated for 3 to 6 months. In MS, the outcome measure in phase II is typically MRI activity. Fenebrutinib is one of several BTK inhibitors that are being tested for MS and it was successful in reducing MRI disease activity by about 90% at 12 weeks compared with placebo. This is promising, since at least 3 similar agents are now in large, phase III trials. These studies should start reporting results next year, and the next few years will be busy with figuring out where these agents fit in MS treatment. Frexalimab is a monoclonal antibody that blocks CD40L, a molecule on the surface of T cells that is important for activation. It successfully reduced MRI activity in a phase II study. This is a novel and interesting approach to MS treatment, and the agent is going into phase III studies soon. On the scientific side, there were several presentations on new results looking at the genetic factors that affect the severity of MS. There has been extensive work on the genetic factors that increase risk of getting MS, with over 200 variants identified. The recent study looked instead for genetic factors for severity, and found one definite variant and several suggestive ones. Several presentations discussed various aspects of this study. This year, there were a large number of presentations on Epstein-Barr virus. Two high profile publications in 2022 have renewed interest in this area. There were presentations on the timing of EBV infection relative to onset of signs of damage to nerve cells and MS symptoms, on human proteins expressed in the brain that might be mistakenly targeted by the anti-EBV immune response, interactions between EBV and other risk factors for MS, detection of EBV in the spinal fluid of people with MS, and the effect of bone marrow transplant on EBV infection among many others. I presented our own work demonstrating that a large proportion of the T lymphocytes in the spinal fluid at the onset of MS are specific for EBV infected cells.
