Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis
Cyrus Daruwalla, Vahid Shaygannejad, Serkan Özakbaş, Eva Havrdová, Dana Horáková, Raed Alroughani, Cavit Boz, Francesco Patti, Marco Onofrj, Alessandra Lugaresi, Sara Eichau, Marc Girard, Alexandre Prat, Pierre Duquette, Bassem Yamout, Samia J. Khoury, Seyed Aidin Sajedi, Recai Türkoğlu, Ayşe Altıntaş, Olga Skibina, Katherine Buzzard, Pierre Grammond, Rana Karabudak, Anneke van der Walt, Helmut Butzkueven, Davide Maimone, Jeannette Lechner‐Scott, Aysun Soysal, Nevin John, Julie Prévost, Daniele Spitaleri, Cristina Ramo‐Tello, Oliver Gerlach, Gerardo Iuliano, Matteo Foschi, Radek Ampapa, Vincent Van Pesch, Michael Barnett, Nevin Shalaby, Marie D’hooghe, Jens Kühle, María José Sá, Marzena J. Fabis‐Pedrini, Allan G. Kermode, Saloua Mrabet, Riadh Gouider, Suzanne Hodgkinson, Guy Laureys, Liesbeth Van Hijfte, Richard Macdonell, Celia Oreja‐Guevara, Edgardo Cristiano, Pamela McCombe, José Luis Sánchez-Menoyo, Bhim Singhal, Yolanda Blanco, Stella Hughes, Justin Garber, Claudio Solaro, Chris McGuigan, Bruce Taylor, Koen de Gans, Mario Habek, Abdullah Al‐Asmi, Simu Mihaela, Tamara Castillo‐Triviño, Talal Al‐Harbi, Juan Ignacio Rojas, Orla Gray, Dheeraj Khurana, Bart Van Wijmeersch, Nikolaos Grigoriadis, Jihad Inshasi, Jiwon Oh, Eduardo Agüera, Yára Dadalti Fragoso, Fraser Moore, Cameron Shaw, Seyed Mohammad Baghbanian, Neil Shuey, Barbara Willekens, Todd A. Hardy, D. Decoo, Ángel Pérez Sempere, Deborah Field, Ray Wynford‐Thomas, Nick Cunniffe, Izanne Roos, Charles B. Malpas, Alasdair Coles, Tomáš Kalinčík, J William L Brown
Abstract
Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS. Methods: We redefined mild relapses in MSBase as ‘non-disabling’, and moderate or severe relapses as ‘disabling’. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00–1.68) or given platform DMTs ( n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15–1.54), but not if given high-efficacy DMTs ( n = 572 vs 3534; HR = 0.90, 95% CI = 0.71–1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.