International Consensus on Smoldering Disease in Multiple Sclerosis using the Delphi Method
Francesca Bagnato1, Antonio Scalfari2, Jiwon Oh3, Laura Airas4, Stefan Bittner5, Massimiliano Calabrese6, Jose Manuel Garcia Dominguez7, Cristina Granziera8, Benjamin Greenberg9, Kerstin Hellwig10, Zsolt Laszlo Illes11, Jan Lycke12, Anthony Traboulsee13, Veronica Popescu14, Gavin Giovannoni15
1Vanderbilt University Medical Center, 2Imperial College, 3St Michael's Hospital, 4University of Turku, 5Johannes Gutenberg- University, 6Clinica Neurologica I, 7Hospital General Universitario Gregorio Marañón, 8Basel University Hospital, 9UT Southwestern, 10St. Josef Hospital Bochum, 11Odense University Hospital, 12University of Gothenburg, 13University of British Columbia, 14Noorderhart Hospital, 15QMUL
Objective:
To develop consensus-driven statements on various domains of smoldering MS: definition, onset, underlying pathology, clinical and radiological manifestations, and modalities to detect smoldering disease in clinical practice. A deeper understanding of smoldering disease will optimize clinical management, foster drug discovery through identification of novel targets and help pwMS understand reasons for their decline.
Background:
Most people with multiple sclerosis (pwMS) experience neurological decline despite suppression of relapses or new lesions. Mounting evidence posits that multiple sclerosis (MS) is not only a disease of focal inflammation, but also involves more diffuse, smoldering pathological processes affecting the whole central nervous system (CNS). Smoldering MS contributes to clinical disease worsening although the underlying biology, clinical and radiological manifestations are yet to be adequately defined.
Design/Methods:
Fifteen MS experts from eight countries across Europe, US, and Canada convened to develop consensus-driven statements on smoldering MS across multiple domains. They employed the Delphi method to anonymously establish agreement on a 5-point scale with “consensus” defined a priori as >75% who agree or strongly agree.
Results:
To date, consensus has been reached on statements related to the domain on definition. Examples are:
- Smoldering disease is considered an umbrella term characterizing chronic pathobiological processes occurring in the CNS, beyond acute focal inflammation, associated with neurodegeneration leading to clinical worsening in pwMS, that may start early and continues throughout the disease course.
- Progression independent of relapse activity (PIRA) should be considered primarily a clinical manifestation of smoldering disease and therefore those terms should not be used interchangeably
Conclusions:
This expert panel aims to provide further recommendations using the Delphi method to help educate the neurology community on smoldering disease and advise on its implementation into routine clinical practice. Full presentation and publication of all statements with supporting evidence is expected in 2023.