Clinical and radiological consequences of delayed therapy escalation in patients with relapsing-remitting multiple sclerosis.

Abstract

Aim of the study: To evaluate the clinical and radiological consequences of delayed escalation of therapy in patients with relapsing-remitting multiple sclerosis (RRMS), in whom, despite finding platform therapy ineffective, high-efficacy drugs were introduced with a delay.

Material and methods: We performed a single-centre, observational study evaluating patients with RRMS for ineffectiveness of disease-modifying therapies (DMTs). Depending on the time of therapy escalation to high-efficacy drugs, the patients were divided into an early escalation or a late escalation group, both of which were then observed for 48 months. All patients underwent a neurological examination every six months and a brain magnetic resonance imaging (MRI) every 12 months. The primary endpoint was a change in the Expanded Disability Status Scale (EDSS) score during the observation period. The secondary endpoint was the time to 6-month confirmed disability progression (6mCDP). In addition, we analysed the annualised relapse rate and the cumulative number of new Gd+ and T2 lesions on brain MRI.

Results: 165 patients were qualified for the analysis. On treatment initiation, mean age was 38 years (± 10.9), and mean EDSS was 1.41 ± 0.38. After 48 months, there was a statistically insignificant decrease in the EDSS score in the early escalation group (-0.17 ± 0.35; p > 0.05), while in the late escalation group there was an increase in the EDSS score. The highest increase was noted in the group in which the escalation was performed with a delay of more than two years (1.2 ± 0.63; p < 0.001), and moreover 80% of patients in this group met the 6mCDP criteria. The median time to 6mCDP was 4.6 years (LESC1) and 4.5 years (LESC2) in the late escalation groups. In the early escalation group, zero subjects met the 6mCDP criteria after 48 months of observation.

Conclusions: In everyday practice, the long-term outcomes in patients with RRMS and disease activity, despite DMT being used, are more favourable after early implementation of high-efficacy drugs. Delaying therapy escalation results in the accumulation of permanent disability in patients with RRMS.