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  • Association of Inflammation and Disability Accrual in Patients With Progressive-Onset Multiple Sclerosis

    Author(s)
    Hughes, Jordana
    Jokubaitis, Vilija
    Lugaresi, Alessandra
    Hupperts, Raymond
    Izquierdo, Guillermo
    Prat, Alexandre
    Girard, Marc
    Duquette, Pierre
    Grand'Maison, Francois
    Grammond, Pierre
    Sola, Patrizia
    Ferraro, Diana
    Ramo-Tello, Cristina
    Trojan, Maria
    Butzkueven, Helmut
    et al.
    Griffith University Author(s)
    Butzkueven, Helmut
    Year published
    2018
    Metadata
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    Abstract
    Importance: The role of inflammatory disease activity as a determinant of disability in progressive-onset multiple sclerosis (MS) remains contested. Objective: To examine the association of superimposed relapses in progressive-onset MS on disease outcomes. Design, Setting, and Participants: Observational cohort study from MSBase, a prospectively collected, international database. Data were collected between January 1995 and February 2017. Analyses began in February 2017. From 44449 patients at time of extraction, 1419 eligible patients (31.9%) were identified for analysis. Inclusion criteria consisted of primary progressive ...
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    Importance: The role of inflammatory disease activity as a determinant of disability in progressive-onset multiple sclerosis (MS) remains contested. Objective: To examine the association of superimposed relapses in progressive-onset MS on disease outcomes. Design, Setting, and Participants: Observational cohort study from MSBase, a prospectively collected, international database. Data were collected between January 1995 and February 2017. Analyses began in February 2017. From 44449 patients at time of extraction, 1419 eligible patients (31.9%) were identified for analysis. Inclusion criteria consisted of primary progressive MS (PPMS) or progressive-relapsing MS (PRMS), adult-onset disease, and minimum data set (including ≥3 visits with disability recorded, ≥3 months between second and last visit). Data were analyzed using multivariable regression models (Andersen-Gill) with mixed effects. Two sensitivity analyses to exclude both relapse-related disability progression and bout-onset progressive MS were performed. Exposures: Grouped according to presence or absence of relapse, defined as an acute episode of clinical worsening. Quantifiable disability change or correlation on imaging was not required to confirm relapse. Main Outcomes and Measures: Cumulative hazard of disability progression. Results: Patients with PRMS were younger than those with PPMS (mean [SD] age, 46 [15] vs 51 [10] years, Cohen d = 0.40) and demonstrated a mean lower Expanded Disability Status Scale score (mean [SD] score, 4.0 [3] vs 4.5 [2.5], Cohen d = 0.28) at inclusion. The ratio of men to women was similar in the PRMS and PPMS groups (252:301 vs 394:472). The overall mean (SD) age was 48 (11) years for men and 50 (10) years for women. Likelihood of confirmed disability progression was lower in patients with superimposed relapses (hazard ratio [HR], 0.83; 95% CI, 0.74-0.94; P =.003). Proportion of follow-up time spent on disease-modifying therapy significantly reduced the hazard of confirmed disability progression in the cohort with relapse (HR, 0.96; 95% CI, 0.94-0.99; P =.01) but not in those without relapse (HR, 1.02; 95% CI, 0.99-1.05; P =.26). When accounting for relapse-related progression, the association of disease-modifying therapy in the cohort with superimposed relapse was no longer observed (HR, 1.10; 95% CI, 0.96-1.24; P =.16). Conclusions and Relevance: In progressive-onset MS, superimposed relapses are associated with a lower risk of confirmed disability progression. This is most likely attributed to the association of disease-modifying therapy with the prevention of relapse-related disability accrual in patients with superimposed relapse. These findings suggest that inflammatory relapses are an important and modifiable determinant of disability accrual in progressive-onset disease.
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    Journal Title
    JAMA Neurology
    Volume
    75
    Issue
    11
    DOI
    https://doi.org/10.1001/jamaneurol.2018.2109
    Subject
    Neurology and neuromuscular diseases
    Neurosciences
    Science & Technology
    Life Sciences & Biomedicine
    Clinical Neurology
    NATURAL-HISTORY
    Publication URI
    http://hdl.handle.net/10072/413794
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