OBJECTIVE: To evaluate variability and predictability of disability trajectories in moderately advanced and advanced multiple sclerosis (MS), and their modifiability with immunomodulatory therapy. METHODS: The epochs between Expanded Disability Status Scale (EDSS) steps 3-6, 4-6 and 6-6.5 were analysed. Patients with relapse-onset MS and having reached 6-month confirmed baseline EDSS step (3/4/6) were identified in MSBase, a global observational MS cohort study. We used multivariable survival models to examine the impact of disease-modifying therapy, clinical and demographic factors on progression to the outcome EDSS step (6/6.5). Sensitivity analyses with varying outcome definitions and inclusion criteria were conducted. RESULTS: For the EDSS 3-6, 4-6 and 6-6.5 epochs, 1560, 1504 and 1231 patients were identified, respectively. Disability trajectories showed large coefficients of variance prebaseline (0.92-1.11) and postbaseline (2.15-2.50), with no significant correlations. The probability of reaching the outcome step was not associated with prebaseline variables, but was increased by higher relapse rates during each epoch (HRs 1.58-3.07; p<0.001). A greater proportion of each epoch treated with higher efficacy therapies was associated with lower risk of reaching the outcome disability step (HRs 0.72-0.91 per 25%; p≤0.02). 3 sensitivity analyses confirmed these results. CONCLUSIONS: Disease progression during moderately advanced and advanced MS is highly variable and amnesic to prior disease activity. Lower relapse rates and greater time on higher efficacy immunomodulatory therapy after reaching EDSS steps 3, 4 and 6 are associated with a decreased risk of accumulating further disability. Highly effective immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced relapse-onset MS.

1st Faculty of Medicine Department of Neurology and Center of Clinical Neuroscience General University Hospital and Charles University Prague Praha Czech Republic

AORN San Giuseppe Moscati Avellino Italy

Assaf Harofeh Medical Center Beer Yaakov Israel

Box Hill Hospital Monash University Melbourne Australia

C Mondino National Neurological Institute Pavia Italy

Cliniques Universitaires Saint Luc Brussels Belgium

Department of Basic Medical Sciences Neuroscience and Sense Organs University of Bari Bari Italy

Department of Biomedical and Neuromotor Sciences University of Bologna and IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna Italy

Department of Medicine University of Melbourne Melbourne Australia

Department of Neurology Amiri Hospital Kuwait City Kuwait

Department of Neurology Donostia University Hospital San Sebastian Spain

Department of Neurology Royal Melbourne Hospital Melbourne Australia

Flinders University and Medical Centre Adelaide Australia

Groen Hart Ziekenhuis Gouda The Netherlands

Hôpital Notre Dame Montreal Canada

Hospital Fernàndez Buenos Aires Argentina

Hospital Germans Trias i Pujol Badalona Spain

Hospital Italiano Buenos Aires Argentina

Hospital Universitario Virgen Macarena Sevilla Spain

Hotel Dieu de Levis Quebec Canada

Hunter Medical Research Institute University of Newcastle Newcastle Australia

Jahn Ferenc Teaching Hospital Budapest Hungary

Karadeniz Technical University Trabzon Turkey

Liverpool Hospital Sydney Australia

Monash School of Medicine Monash University Melbourne Australia

Neuro Rive Sud Hôpital Charles LeMoyne Quebec Canada

Neurology Unit ASUR Marche AV 3 Macerata Italy

Neurology Unit Department of Neuroscience Nuovo Ospedale Civile Sant'Agostino Estense Modena Italy

Ospedali Riuniti di Salerno Salerno Italy

Section of Neurosciences Department NEUROFARBA University of Florence Florence Italy

University Hospital San Carlos IdISSC Madrid Spain

University of Parma Parma Italy

Zuyderland Ziekenhuis Sittard The Netherlands

J Neurol Neurosurg Psychiatry. 2017 Mar;88(3):193. doi: 10.1136/jnnp-2016-314377. PubMed

References provided by Crossref.org

Association of Sustained Immunotherapy With Disability Outcomes in Patients With Active Secondary Progressive Multiple Sclerosis

Management of multiple sclerosis patients in central European countries: current needs and potential solutions