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MRI activity appeared to be a more sensitive measure of disease activity in secondary progressive multiple sclerosis (SPMS) than relapses, an analysis of two datasets showed.

"When we interrogated a large number of people with SPMS, we discovered that what really determines if you have active versus inactive SPMS is how frequently you have an MRI scan," said Gavin Giovannoni, MBBCh, PhD, of Queen Mary University of London in England, who presented the findings at the 2021 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress. "The more frequently you get scanned, the more likely your team is to find new MRI lesions."

"If you rely on having a clinical relapse, you may wait a long time," Giovannoni continued. "For example, after 2 years of no relapse and no MRI activity, disease activity returned in over 50% of previously inactive people with SPMS. However, in four out of five cases, this was driven by MRI activity and not by having a relapse."

SPMS can be categorized as based on evidence of disease activity including relapses and findings on MRI. In their analysis, Giovannoni and colleagues tried to identify how each factor contributed to defining disease activity in SPMS patients by analyzing two datasets: a real-world cohort from the MS disease-specific program (Adelphi MS DSP), and a group of people with SPMS on placebo in the study.

Adelphi MS DSP included 3,580 patients with SPMS surveyed from 2011 to 2019, including 1,889 people categorized with active SPMS (one or more new lesions on the most recent MRI, or one or more relapses in the last 12 months) and 665 people identified as having non-active SPMS.

In this dataset, active SPMS was defined on the basis of MRI lesions in 59.1% of patients, relapse status in 12.6%, and both MRI and relapse in 28.3%.

Active SPMS patients in the Adelphi MS DSP cohort had a lower mean score than non-active patients (4.6 vs 5.2), were more likely to undergo MRI (87.7% vs 58.7%), and had more MRIs per patient (1.24 vs 0.87) in the past 12 months. A greater proportion of people with non-active SPMS were without treatment compared with active SPMS patients (45.1% vs 23.4%).

In the EXPAND trial, disease activity (active SPMS) was defined as presence of relapses in the 2 years prior to screening, with or without one or more gadolinium-enhancing T1 lesions at baseline. Here, 52.6% of participants on placebo (866 people) who had no relapse in the 2 years before screening and no gadolinium-enhancing T1 lesions at baseline were categorized as non-active SPMS.

Among these non-active SPMS patients, more than half became active over follow-up, again driven by MRI: 41.8% had MRI activity only, 4.6% had relapses only, and 9.2% had both MRI and relapse.

"The message is that, in people with non-active secondary progressive multiple sclerosis, if you follow them up and do frequent MRI scans, the majority -- over 50% -- will become active with time," Giovannoni said. "And that depends on MRI frequency. So if you're not scanning these patients frequently, you won't pick up this activity."

"The data highlight the difficulties we have in the MS community in defining active secondary progressive multiple sclerosis and non-active secondary progressive multiple sclerosis reliably," Giovannoni pointed out. "This has negative implications for people with secondary progressive disease and can result in the suboptimal management of these people. We need to think very carefully about how we operationalize and define active and inactive secondary progressive MS clinically."

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