Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis.

Daruwalla, Cyrus Shaygannejad, Vahid Ozakbas, Serkan Havrdova, Eva Kubala Horakova, Dana Alroughani, Raed Boz, Cavit Patti, Francesco Onofrj, Marco Lugaresi, Alessandra Eichau, Sara Girard, Marc Prat, Alexandre Duquette, Pierre Yamout, Bassem Khoury, Samia J Sajedi, Seyed Aidin Turkoglu, Recai Altintas, Ayse Skibina, Olga Buzzard, Katherine Grammond, Pierre Karabudak, Rana van der Walt, Anneke Butzkueven, Helmut Maimone, Davide Lechner-Scott, Jeannette Soysal, Aysun John, Nevin Prevost, Julie Spitaleri, Daniele Ramo-Tello, Cristina Gerlach, Oliver Iuliano, Gerardo Foschi, Matteo Ampapa, Radek Van Pesch, Vincent [UCL] Barnett, Michael Shalaby, Nevin D'hooghe, Marie Kuhle, Jens Sa, Maria Jose Fabis-Pedrini, Marzena Kermode, Allan Mrabet, Saloua Gouider, Riadh Hodgkinson, Suzanne Laureys, Guy Van Hijfte, Liesbeth Macdonell, Richard Oreja-Guevara, Celia Cristiano, Edgardo McCombe, Pamela Sanchez-Menoyo, Jose Luis Singhal, Bhim Blanco, Yolanda Hughes, Stella Garber, Justin Solaro, Claudio McGuigan, Chris Taylor, Bruce de Gans, Koen Habek, Mario Al-Asmi, Abdullah Mihaela, Simu Castillo Triviño, Tamara Al-Harbi, Talal Rojas, Juan Ignacio Gray, Orla Khurana, Dheeraj Van Wijmeersch, Bart Grigoriadis, Nikolaos Inshasi, Jihad Oh, Jiwon Aguera-Morales, Eduardo Fragoso, Yara Moore, Fraser Shaw, Cameron Baghbanian, Seyed Mohammad Shuey, Neil Willekens, Barbara Hardy, Todd A Decoo, Danny Sempere, Angel Perez Field, Deborah Wynford-Thomas, Ray Cunniffe, Nick G Roos, Izanne Malpas, Charles B Coles, Alasdair J Kalincik, Tomas Brown, J William L et al.[show all]

The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. To determine whether early non-disabling relapses predict disability accumulation in RRMS. 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. 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 ( = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( = 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. 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.