Disease-modifying drugs can reduce disability progression in relapsing multiple sclerosis

M.P. Amato, M. Fonderico, E. Portaccio, L. Pastò, L. Razzolini, E. Prestipino, A. Bellinvia, L. Tudisco, R. Fratangelo, G. Comi, F. Patti, G. De Luca, V. Brescia Morra, E. Cocco, C. Pozzilli, P. Sola, R. Bergamaschi, G. Salemi, M. Inglese, E. MillefioriniS. Galgani, M. Zaffaroni, A. Ghezzi, M. Salvetti, G. Lus, C. Florio, R. Totaro, F. Granella, M. Vianello, M. Gatto, G. Di Battista, U. Aguglia, F.O. Logullo, M. Simone, G. Lucisano, P. Iaffaldano, M. Trojano

Research output: Contribution to journalArticlepeer-review


An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18-49 years) and late-onset multiple sclerosis (≥50 years). We included patients with a relapsing-remitting phenotype, ≥5 years follow-up, ≥3 Expanded Disability Status Scale (EDSS) evaluations and a first neurological evaluation within 3 years from the first demyelinating event. Multivariate Cox regression models (adjusted hazard ratio with 95% confidence intervals) were used to assess the risk of reaching a first 12-month confirmed disability worsening and the risk of reaching a sustained EDSS of 4.0. The effect of disease-modifying drugs was assessed as quartiles of time exposure. We found that disease-modifying drugs reduced the risk of 12-month confirmed disability worsening, with a progressive risk reduction in different quartiles of exposure in paediatric-onset and adult-onset patients [adjusted hazard ratios in non-exposed versus exposed >62% of the follow-up time: 8.0 (3.5-17.9) for paediatric-onset and 6.3 (4.9-8.0) for adult-onset, P < 0.0001] showing a trend in late-onset patients [adjusted hazard ratio = 1.9 (0.9-4.1), P = 0.07]. These results were confirmed for a sustained EDSS score of 4.0. We also found that relapses were a risk factor for 12-month confirmed disability worsening in all three cohorts, and female sex exerted a protective role in the late-onset cohort. This study provides evidence that sustained exposure to disease-modifying drugs decreases the risk of disability accumulation, seemingly in a dose-dependent manner. It confirms that the effectiveness of disease-modifying drugs is lower in late-onset patients, although still detectable. © 2020 The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Original languageEnglish
Pages (from-to)3013-3024
Number of pages12
Issue number10
Publication statusPublished - 2020


  • clinical trials
  • clinically isolated syndrome
  • demyelination
  • multiple sclerosis epidemiology
  • neuroinflammation


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