TY - JOUR T1 - Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 196 LP - 203 DO - 10.1136/jnnp-2016-313976 VL - 88 IS - 3 AU - Nathaniel Lizak AU - Alessandra Lugaresi AU - Raed Alroughani AU - Jeannette Lechner-Scott AU - Mark Slee AU - Eva Havrdova AU - Dana Horakova AU - Maria Trojano AU - Guillermo Izquierdo AU - Pierre Duquette AU - Marc Girard AU - Alexandre Prat AU - Pierre Grammond AU - Raymond Hupperts AU - Francois Grand'Maison AU - Patrizia Sola AU - Eugenio Pucci AU - Roberto Bergamaschi AU - Celia Oreja-Guevara AU - Vincent Van Pesch AU - Cristina Ramo AU - Daniele Spitaleri AU - Gerardo Iuliano AU - Cavit Boz AU - Franco Granella AU - Javier Olascoaga AU - Freek Verheul AU - Csilla Rozsa AU - Edgardo Cristiano AU - Shlomo Flechter AU - Suzanne Hodgkinson AU - Maria Pia Amato AU - Norma Deri AU - Vilija Jokubaitis AU - Tim Spelman AU - Helmut Butzkueven AU - Tomas Kalincik Y1 - 2017/03/01 UR - http://jnnp.bmj.com/content/88/3/196.abstract N2 - 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. ER -