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

Abstract

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.

Cost-of-Illness Progression Before and After Diagnosis of Multiple Sclerosis: A Nationwide Register-Based Cohort Study in Sweden of People Newly Diagnosed with Multiple Sclerosis and a Population-Based Matched Reference Group

“…Our study period captures the increasing availability of DMTs, early initiation of which may be associated with maintaining work capacity and a reduced risk of sickness absence or disability pension [ 8 , 9 ]. However, the long-term associations of these DMTs with work capacity or productivity losses remain largely unknown despite improving clinical outcomes [ 60 ]. Nonetheless, the costs of early DMT initiation may potentially be offset by other cost savings [ 61 ].…”

Machine learning classifier to identify clinical and radiological features relevant to disability progression in multiple sclerosis

“…Of these 163 subjects, at baseline 122 patients had a relapsing-remitting form of MS, while the remaining 41 patients had a progressive form. Patients showed a disease duration of 9.90 ± 8.06 years, range [0.00-37.00], with a time between visits that was 3.93 ± 0.95 years, range [2][3][4][5][6]. At the follow-up examination, disease progression was observed in 58 over 163 patients (35.6% of the sample), whose EDSS distributions at baseline and at follow-up were respectively 3.5 [0.0-7.0] and 4.5 [1.5-7.0], while in the remaining 105 patients the EDSS remained stable at 3.0 [0.0-7.5].…”

Multiple Sklerose Therapie Konsensus Gruppe (MSTKG): Positionspapier zur verlaufsmodifizierenden Therapie der Multiplen Sklerose 2021 (White Paper)

“…Aus in den letzten Jahren generierten Registerdaten kann aber bereits jetzt abgeleitet werden, dass DMTs in der Tat das Risiko für eine langfristige neurologische Verschlechterung reduzieren [ 7 , 13 , 42 , 46 , 50 , 51 ]. Der langfristige Nutzen einer Therapie hängt zudem davon ab, wie früh eine DMT begonnen wird [ 3 ].…”