Functional system scores provide a window into disease activity occurring during a multiple sclerosis treatment trial

BACKGROUND: Average expanded disability status scale (EDSS) score on entry into pivotal trials of multiple sclerosis (MS) therapies lies between 2 and 3. These lower EDSS levels are determined by functional system score (FSS). OBJECTIVE: We examined contributions of each FSS to characterization of MS patients at entry to and exit from the pivotal trial of intramuscular interferon β-1a (IM IFN-β-1a), as well as contribution of changes in FSS to changes in EDSS. METHODS: We reviewed FSS and EDSS data collected at 6-month examinations during the IM IFN-β-1a pivotal trial (n = 286). To describe which functional systems were most affected by disease, we used an FSS cutoff of ≥ 2 (mild to moderate impairment) and defined sustained progression as a ≥ 1 point change in EDSS score or FSS being maintained for 6 months. RESULTS: The most frequently involved functional systems at baseline (FSS level of ≥ 2) were cerebellar (38%), pyramidal (37%), and sensory (34%). While all functional systems were affected to some extent by progressing MS, these FSSs were also most often affected at study end, with pyramidal and cerebellar FSSs being the greatest contributors to sustained EDSS progression. Treatment effect with IM IFN-β-1a was most strongly seen in the pyramidal system. CONCLUSION: In this trial, some FSSs contributed more to detection of progression than others. While changes in lower EDSS were heavily weighted by the pyramidal FSS, all of the FSSs appeared to be important in understanding the overall impact of MS progression, demonstrating the responsive nature of the widely utilized EDSS.