Updates from the Evolving Multiple Sclerosis Field: An ECTRIMS 2024 Recap
By Robert Bermel, MD, Director, Cleveland Clinic Mellen Center for Multiple Sclerosis Research and Treatment
The European Committee for Treatment and Research in MS ( ECTRIMS ) annual meeting has become the largest annual worldwide gathering of experts in multiple sclerosis (#MS) and related disorders.
ECTRIMS 2024 was held September 18-20, 2024, in Copenhagen Denmark, and kicked off with a tribute to the Queen of Denmark, who has been an advocate for MS research throughout her career. Denmark has one of the highest incidences of MS per capita in the world. The queen, along with thousands of attendees in the opening session of the congress, watched a retrospective documentary reflecting on 40 years of ECTRIMS history. From small but ambitious beginnings, the conference has grown to over 8,000 attendees.
For the first time, an ECTRIMS pre-day meeting was organized, focusing on pediatric MS, neuromyelitis optica spectrum disorder (#NMOSD), myelin oligodendrocyte glycoprotein antibody disorder (#MOGAD) and autoimmune encephalitis and immunotherapy complications. The expanding world of diagnostic and treatment tools for these rare but complex disorders necessitates a day dedicated to their treatment and research. A section on biomarkers was co-chaired by Cleveland Clinic autoimmune neurology expert Amy Kunchok, MD, PhD.
One of the most anticipated sessions was the official announcement of the updated diagnostic criteria for MS, presented on behalf of the International Panel by Professor Xavier Montalban , MD, PhD from the CEMCAT (Centre d'Esclerosi Múltiple de Catalunya) in Barcelona, Spain. Highlights include the use of central vein sign and paramagnetic rim lesions as imaging biomarkers to support the diagnosis, integration of the optic nerve as a fifth topography in MS diagnosis and the ability to make a diagnosis in an asymptomatic patient. The new diagnostic criteria represent a shift toward a more biologically-based diagnosis rather than relying on multiple events over time plus physical exam findings. Key data for the central vein sign incorporation were contributed by the multicenter CAVS-MS study, led by Daniel Ontaneda , MD, PhD from Cleveland Clinic.
The other major anticipated reports were the Phase 3 trial results from tolebrutinib – the HERCULES and GEMINI trials. Robert Fox , MD, presented the results of the HERCULES trial of tolebrutinib in non-relapsing secondary progressive MS, showing a 31% reduction in risk of 6-month confirmed disability progression in those on tolebrutinib compared to those on placebo. There was also a significant increase in confirmed disability improvement (CDI), 10% of tolebrutinib patients improved on EDSS vs 5% on placebo.
Jiwon Oh , MD, PhD, from St. Michael's Hospital in Toronto presented the results of the GEMINI I and II trials of tolebrutinib vs teriflunomide in relapsing MS, which did not meet their primary outcome measure of reduced relapse rate vs. teriflunomide. However, there was a consistent effect across trials of reducing risk of 6-month and 3-month confirmed disability progression, with tolebutinib showing less benefit than teriflunomide on T1 gadolinium-enhancing lesions.
Some factors, including a lack of slowing of brain volume loss in HERCULES and seemingly no benefit beyond teriflunomide in suppressing new MRI lesions, leave questions about the potential mechanism of disability prevention. There is a risk of liver toxicity with BTK inhibitors, as 0.5% of participants in the tolebrutinib group of the HERCULES trial experienced peak ALT increases of >20x ULN, all occurring within the first 90 days of treatment and most resolving without sequelae. One participant on tolebrutinib received a liver transplant and died due to post-operative complications. Since then, enhanced liver safety monitoring has been included in the first 90 days to prevent episodes of severe toxicity. Future analyses of the HERCULES and GEMINI trials including subgroup analyses will hopefully lead to improved understanding of the mechanisms of progressive disability accumulation in MS, and how to safely utilize this medication in the population that has the best chance to benefit.
Overall, the focus on progressive MS prompted hallway discussions of the need for an evolution of outcome measures, to more sensitively capture and measure progression, to support improved clinical trials and clinical care. The next major MS meeting will be Americas Committee for Treatment & Research in Multiple Sclerosis (ACTRIMS) Forum 2025, in West Palm Beach, Florida February 27 - March 1, 2025.