Relapsing multiple sclerosis patients treated with disease modifying therapy exhibit highly variable disease progression: A predictive model

• Our model identifies moderately severe MS patients and predicts further worsening.
• We describe three unique, separate patterns of disability.
• Our progressive phenotypes represent a useful dichotomy of secondary progressive MS.
• Onset of accelerated worsening of MS occurs at any point in the first two decades.

ObjectiveTo describe a “new natural history” of multiple sclerosis (MS), characterizing three patterns of progression in Relapsing MS (RMS) patients during the “treatment era,” using newly developed definitions. By utilizing our simple model we intend to predict which patients are most likely to reach an EDSS of 6.0.MethodsWe stratified MS progression into three distinct patterns: aggressive MS (AMS), intermediate MS (IMS) and mild MS (MMS), based on Expanded Disability Status Scale (EDSS) score rate of change. These groups were compared for progression of EDSS before and after reaching these definitions.ResultsThe three groups remained significantly different in terms of disability throughout their disease courses p ≤ 0.001; 98% of the patients used disease modifying treatments (DMTs). AMS patients represent a significantly more disabling and aggressive form of MS than the IMS group.ConclusionsTransition from relatively mild MS to aggressive course may begin at any time in the first 15 years, despite DMTs. Our definition for AMS is unique and identifies a group of patients who become permanently disabled within two years after a variable amount of time in a benign phase, despite treatment with modern DMTs.