Acute Clinical Events Identified as Relapses With Stable Magnetic Resonance Imaging in Multiple Sclerosis
Authors: Antoine Gavoille, Fabien Rollot, Romain Casey, Anne Kerbrat, Emmanuelle Le Page, Kevin Bigaut, Guillaume Mathey, Laure Michel, Jonathan Ciron, Aurelie Ruet, Elisabeth Maillart, Pierre Labauge, Hélène Zephir, Caroline Papeix, Gilles Defer, Christine Lebrun-Frenay, Thibault Moreau, Eric Berger, Bruno Stankoff, Pierre Clavelou, Eric Thouvenot, Olivier Heinzlef, Jean Pelletier, Abdullatif Al-Khedr, Olivier Casez, Bertrand Bourre, Philippe Cabre, Abir Wahab, Laurent Magy, Jean-Philippe Camdessanché, Inès Doghri, Solène Moulin, Haifa Ben-Nasr, Céline Labeyrie, Karolina Hankiewicz, Jean-Philippe Neau, Corinne Pottier, Chantal Nifle, Eric Manchon, Bertrand Lapergue, Sandrine Wiertlewski, Jérôme De Sèze, Sandra Vukusic, David Axel Laplaud, François Cotton, Pascal Douek, Francis Guillemin, Alexandre Pachot, Javier Olaiz, Claire Rigaud-Bully, Romain Marignier, Guillaume Mathey, Anne Kerbrat, Damien Biotti, Jean-Christophe Ouallet, Nicolas Collongues, Olivier Outteryck, Xavier Moisset, Nathalie Derache, Mikaël Cohen, Agnès Fromont, Sandrine Wiertlewsky, Matthieu Bereau, Bertrand Audoin, Claire Giannesini, Caroline Bensa, Giovanni Castelnovo, Ombeline Fagniez, Benjamin Hebant, Mathieu Vaillant, Séverine Jeanin, Alain Créange, Jean-Michel Vallat, Philippe Convers, Stéphane Beltran, Céline Labeyrie, Carole Henry, Marie Camuzeaux, Maryline Delattre, Laura Trotta, Catherine Girod, Amandine Ostermann-Ziegler, Damien Le Port, Noellie Freitas, Carole Berthe, Katy-Kim Lataste, Karima Zehrouni, Frédéric Pinna, Julie Petit, Sadou Safa Diallo, Karine Droulon, Céline Callier, Alexia Protin, Melinda Moyon, Chrystelle Cappe, Emilie Dumont, Hanane Agherbi, Marie Blanchere, Marie-Pierre Ranjeva, Amandine Da Veiga, Maty Diop Kane, Christine Vimont, Marjory Cayol, Safiyatou Balde, Daisy Rousseau, Karine Ferraud, Géraldine Meunier, Elise Varnier, Edwige Lescieux, Halima Bourenane, Stéphanie Cossec, Emilie Rabois, Lynda Benammar, Anaïs Beulaygue
Journal: JAMA Neurology (2024)

Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development. To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI). This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection. Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise. Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated. Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs. The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.