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

Importance

Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development.

Objective

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).

Design, Setting, and Participants

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.

Exposures

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.

Main Outcomes and Measures

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.

Results

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.

Conclusions and Relevance

The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.