Timed 25 foot walk (T25FW) and 9-hole peg test (9HPT) may be more reliable clinical outcomes measures in patients with secondary progressive multiple sclerosis (SPMS), compared with the expanded disability status scale (EDSS), according to study results published in Neurology.
Limited data are available on the reliability of clinical outcome measures beyond EDSS in patients with SPMS. The objective of this study was to assess the reliability of clinical outcomes in SPMS trials by using data from the placebo arms two randomized, controlled trials.
Both IMPACT and ASCEND were randomized, double-blind, placebo-controlled trials that evaluated interferon beta 1a and natalizumab treatment, respectively, in patients with SPMS. Disability progression and improvement rates were determined by comparing baseline and follow-up disability measures. They were defined as worsening or improvement, respectively, of at least 20 percent from baseline in time for the T25FW and the 9HPT. Worsening or ‘improvement’ on the EDSS was defined as an increase or decrease, respectively, of 1 whole point on the EDSS if the baseline EDSS was 5.5 or lower, and of 0.5 points if the baseline EDSS was 6.0 or 6.5. A progression event was classified as sustained if it was confirmed at 3 months and at the last visit.
According to data on 219 patients from the IMPACT dataset and 449 patients from the ASCEND dataset, disability generally increased steadily over time on every measure. In both datasets, the EDSS displayed the highest rates of ‘improvement’ over time; additionally, it showed the smallest difference between ‘improvement’ rates and disability progression.
Disability progression rates for the T25FW and 9HPT steadily increased throughout the study. ‘Improvement rates’ for both remained at no more than 10%. For the EDSS, ‘improvement’ rates increased, paralleling disability progression rates throughout the trial. This difference was more prominent in the IMPACT dataset than in the ASCEND dataset.
“All investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS,” concluded the study researchers.
Koch MW, Mostert J, Repovic P, Bowen JD, Uitdehaag B, Cutter G. Reliability of outcome measures in clinical trials in secondary progressive multiple sclerosis. Neurology. Published online October 26, 2020. doi:10.1212/WNL.0000000000011123