PT  - JOURNAL ARTICLE
AU  - Kalincik, Tomas
AU  - Diouf, Ibrahima
AU  - Sharmin, Sifat
AU  - Malpas, Charles
AU  - Spelman, Tim
AU  - Horakova, Dana
AU  - Havrdova, Eva Kubala
AU  - Trojano, Maria
AU  - Izquierdo, Guillermo
AU  - Lugaresi, Alessandra
AU  - Prat, Alexandre
AU  - Girard, Marc
AU  - Duquette, Pierre
AU  - Grammond, Pierre
AU  - Jokubaitis, Vilija
AU  - van der Walt, Anneke
AU  - Grand'Maison, Francois
AU  - Sola, Patrizia
AU  - Ferraro, Diana
AU  - Shaygannejad, Vahid
AU  - Alroughani, Raed
AU  - Hupperts, Raymond
AU  - Terzi, Murat
AU  - Boz, Cavit
AU  - Lechner-Scott, Jeannette
AU  - Pucci, Eugenio
AU  - Van Pesch, Vincent
AU  - Granella, Franco
AU  - Bergamaschi, Roberto
AU  - Spitaleri, Daniele
AU  - Slee, Mark
AU  - Vucic, Steve
AU  - Ampapa, Radek
AU  - McCombe, Pamela
AU  - Ramo-Tello, Cristina
AU  - Prevost, Julie
AU  - Olascoaga, Javier
AU  - Cristiano, Edgardo
AU  - Barnett, Michael
AU  - Saladino, Maria Laura
AU  - Sanchez-Menoyo, Jose Luis
AU  - Hodgkinson, Suzanne
AU  - Rozsa, Csilla
AU  - Hughes, Stella
AU  - Moore, Fraser
AU  - Shaw, Cameron
AU  - Butler, Ernest
AU  - Skibina, Olga
AU  - Gray, Orla
AU  - Kermode, Allan
AU  - Csepany, Tunde
AU  - Singhal, Bhim
AU  - Shuey, Neil
AU  - Piroska, Imre
AU  - Taylor, Bruce
AU  - Simo, Magdolna
AU  - Sirbu, Carmen-Adella
AU  - Sas, Attila
AU  - Butzkueven, Helmut
AU  - ,
TI  - Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years
AID  - 10.1212/WNL.0000000000011242
DP  - 2021 Feb 02
TA  - Neurology
PG  - e783--e797
VI  - 96
IP  - 5
4099  - http://n.neurology.org/content/96/5/e783.short
4100  - http://n.neurology.org/content/96/5/e783.full
SO  - Neurology2021 Feb 02; 96
AB  - Objective To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.Methods We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.Results A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43–0.82, p = 0.0016), worsening of disability (0.56, 0.38–0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19–0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50–0.70, p = 10−9) and worsening of disability (0.81, 0.67–0.99, p = 0.043).Conclusion Continued treatment with MS immunotherapies reduces disability accrual by 19%–44% (95% CI 1%–62%), the risk of need of a walking aid by 67% (95% CI 41%–81%), and the frequency of relapses by 40–41% (95% CI 18%–57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.Classification of Evidence This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.CI=confidence interval; EDSS=Expanded Disability Status Scale; HR=hazard ratio; MS=multiple sclerosis; NNT=number needed to treat