By Lucy Piper, Senior medwireNews Reporter
Researchers recommend extending the minimum timeframe for confirming disability progression in multiple sclerosis (MS) from 3–6 months to 12 or 24 months to better distinguish true irreversible disability from relapse-associated transient disability.
The recommendation is based on their finding that a 3–6 month confirmation period overestimated the accumulation of permanent disability by up to 30%, compared with up to 20% and 11% if a 12-or 24-month period is used, respectively.
“This could lead to spurious results in short-term clinical trials, and the issue may be magnified further in cohorts consisting predominantly of younger patients and patients with relapse-remitting disease,” says the team.
Led by Tomas Kalincik (Royal Melbourne Hospital, Australia), the researchers used the global MSBase registry to evaluate 48 criteria for disability progression in 16,636 patients with MS who had a minimum of three Expanded Disability Status Scale (EDSS) scores recorded.
The median time between EDSS visits was 6.6 months and the cumulative captured follow-up was 112,584 patient–years, with a median follow-up per patient of 5.7 years.
Progression rates varied between 0.41 and 1.14 events per patient-decade with only 17.3% of progression events identified by all 48 criteria simultaneously.
Over the subsequent 5 years, disability regressed in 11% to 34% of the progression events. The length of the disability confirmation period was the most important determinant, with the proportion of events regressing within 5 years decreasing with longer confirmation time, from 30% at 3 months to 26% at 6 months, 20% at 12 months and 11% at 24 months.
Indeed, a 12- or 24-month confirmed progression of disability combined with a baseline EDSS recorded at a single timepoint provided the most stable criteria for detecting disability progression and persistence at 5 years, correctly identifying 80–81% and 88–89% of persistent progression events, respectively. The two-strata and three-strata EDSS criteria for determining the magnitude of progression were comparable for identifying persistent progression events.
The researchers note in Brain that progression events confirmed for 3 months were the least persistent, with 22–26% of such events regressing over the initial 10 years after progression, compared with just 8–9% of those confirmed over a 24-month period.
Other factors increasing the likelihood of a progressive disability event were male gender, older age, progressive MS and a lower EDSS score, while regression of disability was more likely to occur among women, younger individuals and those with a relapse–remitting disease course.
Given their findings, Kalincik and colleagues recommend “implementation of longer disability confirmation period in the design of observational studies but also of prospective clinical trials.”
They add: “This is not impractical as most modern trials include open-label extension studies, and these observations can be used to define 12- and 24-month confirmations of disability progression events which occurred during the randomised stages of these trials.”
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