Assessment of definitions of sustained disease progression in relapsing-remitting multiple sclerosis

Area of Science:

• Neurology
• Clinical Trials
• Disease Progression Research

Background:

• Sustained progression on the Expanded Disability Status Scale (EDSS) is a standard outcome in Multiple Sclerosis (MS) clinical studies.
• However, the EDSS may not reliably capture long-term, irreversible disease progression.
• Alternative or refined measures are needed to accurately assess disability accumulation in MS.

Purpose of the Study:

• To evaluate the performance of various definitions of sustained progression in patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome.
• To assess the impact of relapses and changes in healthcare providers on the probability of maintaining sustained progression.
• To determine if functional system (FS) scales offer a more sensitive measure of irreversible disability compared to the EDSS.

Main Methods:

• Included patients diagnosed with RRMS or clinically isolated syndrome with evidence of brain MRI lesions.
• Investigated fifteen distinct definitions of sustained progression using both EDSS and FS scales.
• Analyzed the influence of relapses and provider changes on sustained progression outcomes, noting provider access to prior EDSS scores.

Main Results:

• Between 15.8% and 42.2% of patients met definitions of sustained progression based on EDSS.
• Nearly 50% of patients who initially showed progression did not maintain it throughout the follow-up period.
• Progression was most frequent on pyramidal and sensory FS scales, but these did not prove more sensitive to irreversible disability.

Conclusions:

• Short-term fluctuations in EDSS or FS scores may not accurately indicate irreversible disability in RRMS.
• Current definitions of sustained progression may be unreliable for assessing long-term irreversible changes in MS.
• Further research is needed to develop more robust outcome measures for irreversible disability in MS clinical trials.