Disease-modifying drugs can reduce disability progression in relapsing multiple sclerosis.
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.
['Amato|Maria Pia|MP|', 'Fonderico|Mattia|M|', 'Portaccio|Emilio|E|', 'Pastò|Luisa|L|', 'Razzolini|Lorenzo|L|', 'Prestipino|Elio|E|', 'Bellinvia|Angelo|A|', 'Tudisco|Laura|L|', 'Fratangelo|Roberto|R|', 'Comi|Giancarlo|G|', 'Patti|Francesco|F|', 'De Luca|Giovanna|G|', 'Brescia Morra|Vincenzo|V|', 'Cocco|Eleonora|E|', 'Pozzilli|Carlo|C|', 'Sola|Patrizia|P|', 'Bergamaschi|Roberto|R|', 'Salemi|Giuseppe|G|', 'Inglese|Matilde|M|', 'Millefiorini|Enrico|E|', 'Galgani|Simonetta|S|', 'Zaffaroni|Mauro|M|', 'Ghezzi|Angelo|A|', 'Salvetti|Marco|M|', 'Lus|Giacomo|G|', 'Florio|Ciro|C|', 'Totaro|Rocco|R|', 'Granella|Franco|F|', 'Vianello|Marika|M|', 'Gatto|Maurizia|M|', 'Di Battista|Giancarlo|G|', 'Aguglia|Umberto|U|', 'Logullo|Francesco Ottavio|FO|', 'Simone|Marta|M|', 'Lucisano|Giuseppe|G|', 'Iaffaldano|Pietro|P|', 'Trojano|Maria|M|']
D000328:Adult D018501:Antirheumatic Agents D015331:Cohort Studies D006233:Disabled Persons D018450:Disease Progression D005260:Female D005500:Follow-Up Studies D006801:Humans D007558:Italy D008297:Male D008875:Middle Aged D020529:Multiple Sclerosis, Relapsing-Remitting D011446:Prospective Studies D012189:Retrospective Studies
clinical trials demyelination clinically isolated syndrome multiple sclerosis epidemiology neuroinflammation