Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years. (2nd February 2021)

• Record Type: Journal Article
• Authors: Kalincik, Tomas; Diouf, Ibrahima; Sharmin, Sifat; Malpas, Charles; Spelman, Tim; Horakova, Dana; Havrdova, Eva Kubala; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Grammond, Pierre; Jokubaitis, Vilija; van der Walt, Anneke; Grand'Maison, Francois; Sola, Patrizia; Ferraro, Diana; Shaygannejad, Vahid; Alroughani, Raed; Hupperts, Raymond; Terzi, Murat; Boz, Cavit; Lechner-Scott, Jeannette; Pucci, Eugenio; Van Pesch, Vincent; Granella, Franco; Bergamaschi, Roberto; Spitaleri, Daniele; Slee, Mark; Vucic, Steve; Ampapa, Radek; McCombe, Pamela; Ramo-Tello, Cristina; Prevost, Julie; Olascoaga, Javier; Cristiano, Edgardo; Barnett, Michael; Saladino, Maria Laura; Sanchez-Menoyo, Jose Luis; Hodgkinson, Suzanne; Rozsa, Csilla; Hughes, Stella; Moore, Fraser; Shaw, Cameron; Butler, Ernest; Skibina, Olga; Gray, Orla; Kermode, Allan; Csepany, Tunde; Singhal, Bhim; Shuey, Neil; Piroska, Imre; Taylor, Bruce; Simo, Magdolna; Sirbu, Carmen-Adella; Sas, Attila; Butzkueven, Helmut;
• Other Names: author non-byline.; Iuliano Gerardo author non-byline.; Petersen Thor author non-byline.; Verheul Freek author non-byline.; Vella Norbert author non-byline.; Kovacs Krisztina author non-byline.; PetkovskaBoskova Tatjana author non-byline.; Erdelyi Tunde author non-byline.; Dobos Eniko author non-byline.; Bolaños Ricardo Fernandez author non-byline.; Kister Ilya author non-byline.; Cabrera-Gomez Jose Antonio author non-byline.; Roullet Etienne author non-byline.; Zwanikken Cees author non-byline.; Den Braber-Moerland Leontien author non-byline.; Der Norma author non-byline.; Firstenfeld Alfredo author non-byline.; Bacile Elizabeth Alejandra author non-byline.; Santiago Vetere author non-byline.; Vrech S Carlos author non-byline.; Hardy Todd author non-byline.; Arruda Walter Oleschko author non-byline.; Charest Stephane author non-byline.; Oreja-Guevara Celia author non-byline.; McDonnell Gavin author non-byline.; Rum Gabor author non-byline.; Flechter Shlomo author non-byline.; Khurana Dheeraj author non-byline.; Amato Maria Pia author non-byline.; Bojkovski Vladimir author non-byline.; van Munster Erik author non-byline.; Rio Maria Edite author non-byline.; Al-Harbi Talal author non-byline.; Haartsen Jodi author non-byline.;
• Is Part Of: Neurology. Volume 96:Number 5(2021)
• Page Start: e783
• Page End: e797
• Publication Date: 2021-02-02
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000011242
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : 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.