Background

There is a growing need to identify the course of aggressive multiple sclerosis (agMS) at an early stage so that affected patients can be treated with suitable disease modifying drugs (DMD). Investigations of treatment patterns in agMS and non-agMS patients are of interest, particularly in the context of the multitude of agMS definitions.

Objectives

We aimed to determine characteristics of DMDs at baseline for comparative analyses of agMS patients and non-agMS patients.

Methods

We included patients from the German Multiple Sclerosis registry who started DMD use between 2010 and 2020 and were assessable on whether they are agMS patients according to a commonly used criterium of reaching EDSS ≥6.0, or by a criterium for highly active MS, i.e. ≥2 relapses during 12 months, or gd+ lesions on MRI. Both were assessed within the first 5 years of disease duration.

Results

7249 patients fulfilled the inclusion criteria. Of these, 860 were identified as agMS. In agMS patients, Interferons (INFs) were the most frequently used DMDs with 34.8% followed by Glatiramer acetate (GLAT, 24.0%), Dimethyl fumarate (DMF, 15.8%), Teriflunomide (TRF, 7.6%), Natalizumab (NTZ, 5.4%), Fingolimod (FTY, 3.9%), Ocrelizumab (OCR, 3.2%), Steroids (STE, 1.8%), and others (3.5%). Regarding patients with non-agMS, INFs were also most frequent with 30.5% followed by GLAT (18.1%), DMF (13.2%), FTY (8.1%), NTZ (7.7%), TRF (7.5%), OCR (5.9%), STE (2.3%), and others (6.7%).

Within 5 years of disease duration, switches to another DMD were observed for 51% of agMS patients whereas only 17% of non-agMS switched to a second DMD. The average time spent on the first DMD was 1.3 (±1.1) years for agMS patients and 3.4 (±3.6) years for non-agMS patients (p<0.001; Mann-Whitney test). With regard to DMD use, significant differences between agMS and non-agMS patients were detected (p<0.001; χ²-test): INFs (p=0.009), GLAT (p<0.001) and DMF (p=0.03) were used significantly more often by agMS patients while FTY (p<0.001), NTZ (p=0.02) and OCR (p=0.002) were used more often by non-agMS patients.

Conclusions

Our analysis showed that in line with the (national) guidelines, the new immunomodulatory treatments are accessible to all MS patients. The patients classified as agMS spent less time on the first DMD than non-agMS patients did. To investigate causal factors in the connection between DMD preference and resulting disease progression, Marginal Structural Models are required, adjusting for relevant time-varying confounders such as patient demography, clinical visit details, MRI, and relapse parameters.