Association of Early Progression Independent of Relapse Activity With Long-term Disability After a First Demyelinating Event in Multiple Sclerosis

Author:

Tur Carmen1,Carbonell-Mirabent Pere1,Cobo-Calvo Álvaro1,Otero-Romero Susana1,Arrambide Georgina1,Midaglia Luciana1,Castilló Joaquín1,Vidal-Jordana Ángela1,Rodríguez-Acevedo Breogán1,Zabalza Ana1,Galán Ingrid1,Nos Carlos1,Salerno Annalaura2,Auger Cristina2,Pareto Deborah2,Comabella Manuel1,Río Jordi1,Sastre-Garriga Jaume1,Rovira Àlex2,Tintoré Mar1,Montalban Xavier1

Affiliation:

1. Multiple Sclerosis Centre of Catalonia, Department of Neurology/Neuroimmunology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

2. Section of Neuroradiology, Department of Radiology, Vall d’Hebron University Hospital, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain

Abstract

ImportanceProgression independent of relapse activity (PIRA) is the main event responsible for irreversible disability accumulation in relapsing multiple sclerosis (MS).ObjectiveTo investigate clinical and neuroimaging predictors of PIRA at the time of the first demyelinating attack and factors associated with long-term clinical outcomes of people who present with PIRA.Design, Setting, and ParticipantsThis cohort study, conducted from January 1, 1994, to July 31, 2021, included patients with a first demyelinating attack from multiple sclerosis; patients were recruited from 1 study center in Spain. Patients were excluded if they refused to participate, had alternative diagnoses, did not meet protocol requirements, had inconsistent demographic information, or had less than 3 clinical assessments.ExposuresExposures included (1) clinical and neuroimaging features at the first demyelinating attack and (2) presenting PIRA, ie, confirmed disability accumulation (CDA) in a free-relapse period at any time after symptom onset, within (vs after) the first 5 years of the disease (ie, early/late PIRA), and in the presence (vs absence) of new T2 lesions in the previous 2 years (ie, active/nonactive PIRA).Main Outcomes and MeasuresExpanded Disability Status Scale (EDSS) yearly increase rates since the first attack and adjusted hazard ratios (HRs) for predictors of time to PIRA and time to EDSS 6.0.ResultsOf the 1128 patients (mean [SD] age, 32.1 [8.3] years; 781 female individuals [69.2%]) included in the study, 277 (25%) developed 1 or more PIRA events at a median (IQR) follow-up time of 7.2 (4.6-12.4) years (for first PIRA). Of all patients with PIRA, 86 of 277 (31%) developed early PIRA, and 73 of 144 (51%) developed active PIRA. Patients with PIRA were slightly older, had more brain lesions, and were more likely to have oligoclonal bands than those without PIRA. Older age at the first attack was the only predictor of PIRA (HR, 1.43; 95% CI, 1.23-1.65; P < .001 for each older decade). Patients with PIRA had steeper EDSS yearly increase rates (0.18; 95% CI, 0.16-0.20 vs 0.04; 95% CI, 0.02-0.05; P < .001) and an 8-fold greater risk of reaching EDSS 6.0 (HR, 7.93; 95% CI, 2.25-27.96; P = .001) than those without PIRA. Early PIRA had steeper EDSS yearly increase rates than late PIRA (0.31; 95% CI, 0.26-0.35 vs 0.13; 95% CI, 0.10-0.16; P < .001) and a 26-fold greater risk of reaching EDSS 6.0 from the first attack (HR, 26.21; 95% CI, 2.26-303.95; P = .009).Conclusions and RelevanceResults of this cohort study suggest that for patients with multiple sclerosis, presenting with PIRA after a first demyelinating event was not uncommon and suggests an unfavorable long-term prognosis, especially if it occurs early in the disease course.

Publisher

American Medical Association (AMA)

Subject

Neurology (clinical)

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