Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis
Authors: 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 , 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 
Published: March 2023

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.