An international panel has developed consensus-driven statements on smoldering disease (SD) in multiple sclerosis (MS), including domains such as definition, onset, pathology, clinical and imaging manifestations, and detection modalities. The goal of the panel is to educate the neurology community about SD with the aim of encouraging further research, optimizing the clinical management of individuals with MS, and promoting drug discovery and development. The statements were presented at the 9th joint meeting of the European and American Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS).

The panel consisted of 15 MS experts from 8 countries in Europe and North America and used Delphi methodology to develop consensus statements based on a 5-point scale of agreement. The panel defined consensus as occurring when more than 75% of participants either “agreed” or “strongly agreed” on a given statement. Consensus was reached on all statements, with the panel agreeing that SD:

• Consists of chronic pathobiological processes
• Starts early, driving cognitive and physical deterioration
• Can be present despite a lack of clinical or subclinical activity

According to the panel, SD is most likely driven by brain and spinal cord atrophy resulting from chronic active lesions, microglia activation, and focal and global cortical pathology. The panel agreed that the current model of clinical care for MS relies too heavily on relapses and new MRI activity to identify disease activity, limiting clinical care. The consensus statements urged for the implementation of patient-reported outcomes, wearable devices, and further measures to evaluate SD-associated MS worsening more comprehensively.

Among the international panel were experts from Imperial College London, Vanderbilt University Medical Center, St. Michael’s Hospital, the University of Turku, Johannes Gutenberg University, Clinica Neurological I, Georgorio Marañón General University Hospital, the University of Basel, the University of Texas Southwestern, St. Josef Hospital, Odense University Hospital, the University of Gothenburg, Noorderhart Hospital, the University of British Columbia, the Blizard Institute of Queen Mary’s University of London. This project was initiated through funding from and meetings facilitated by Sanofi.