Identifying markers for progression to secondary MS could transform management strategies for MS, according to data reported at ECTRIMS and described in this article first published Oct. 17, 2021 and republished here as part of BreakingMED’s year-end review of clinical news. Click here to view the original version and obtain CME/CE credit for the activity.
The presence of cortical lesions at diagnosis in patients with multiple sclerosis proved to be strongly predictive of conversion to secondary progressive MS (SPMS) and disability in a study of patients followed for almost two decades.
Researchers followed 207 MS patients who underwent brain MRI imaging and clinical assessment at diagnosis, with a mean time from symptom onset of two years. The assessments were repeated periodically throughout a median of 17 years of follow-up, and the majority of study participants (n=180) also underwent lumbar puncture.
The study showed a correlation between the number of cortical lesions identified by MRI at diagnosis and the progression to secondary progressive disease and disability years later.
Having more than three cortical lesions identified by MRI at diagnosis was strongly correlated with later disability, as measured by the Expanded Disability Status Scale (EDSS), with the main EDSS score at follow-up being 6.0 in patients who progressed to SPMS, compared to 2.0 among patients who did not.
The study was one of several involving secondary progressive MS patients presented at the virtual 37th Congress of the European Committee for Treatment and Research in MS—ECTRIMS 2021—held Oct. 13-15.
Only 9 patients had no brain T2 MRI lesions at diagnosis, 129 had one to 10 lesions, and 79 patients had more than 10 T2 lesions.
Among patients classified as having secondary progressive MS, roughly 84% had more than three multicortical lesions at diagnosis, while roughly 16% had less than three lesions. Among those classified as relapsing remitting MS or clinically isolated syndrome (CIS), just 10% had more than three lesions, 28% had one to three lesions, and 62% had no lesions at diagnosis.
Another SPMS study presented at ECTRIMS 2021 highlighted the pitfalls of categorizing the disorder as either active or non-active based on relapses alone.
Based on their analysis of real-world and clinical studies, the researchers concluded that magnetic resonance imaging (MRI) is a more sensitive measure of disease activity than relapse.
Professor of neurology Gavin Giovannoni, MBBCh, PhD, of the London School of Medicine and Dentistry, noted in a video presentation that repeated MRI most often identified progression from non-active to active SPMS in both real-world and clinical trial cohorts.
“The message really is that in people with non-active SPMS, if you follow them and do frequent MRI, the majority—more than 50%—will become active with time,” he said. “If you aren’t scanning these patients frequently, you won’t pick up this disease activity.”
The analysis included real-world data from the Adelphi real-world MS Disease Specific Programme (Adelphi MS DSP) and the phase III EXPAND study.
In the real-world cohort, utilization of MRI was found to be much lower in patients classified as non-active SPMS compared to those classified as active SPMS, and this resulted in fewer chances to detect shifting disease activity, Giovannoni said.
In the EXPAND analysis, disease activity was identified by repeated MRI in more than half of participants classified as non-active SPMS in the placebo arm of the study.
“I think the data highlight the difficulty we have as an MS community in reliably defining active secondary progressive multiple sclerosis and non-active secondary progressive multiple sclerosis, and this has negative implications for people with secondary progressive disease,” Giovannoni said.
“This can result in the sub-optimal management of these people, and I think we need to think very carefully about how we operationalize and define active and inactive secondary progressive MS clinically.”
Treatment with the disease modifying therapy natalizumab (Tysarbri) was found to reduce disease progression of patients with secondary progressive disease in newly reported data on patients with both active and non-active disease enrolled in pharmaceutical company Biogen’s two-part, randomized, phase III ASCEND study
In previously reported study findings, treatment with natalizumab failed to reduce progression in the initial phase of the trial, with progression measured by the primary study endpoint of composite Expanded Disability Status Score (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT).
In the newly reported analysis, which included the ASCEND intention-to-treat population (439 natalizumab-treated, 448 placebo-treated patients), the researchers identified patients with non-active or low active SPMS.
The odds of progression to disability in these patients, assessed by 9HPT, favored natalizumab over placebo (OR range, 0.50-0.53) with the upper limits of the credible intervals <1.00.
“Over 96 weeks, in patients without acute MRI activity based on principal stratum analysis by new or newly enlarging T2 lesions per year, the odds of disease progression assessed by 9HPT favored natalizumab over placebo (PR range, 0.57-0.76), although the upper limits of the credible intervals were >1.00, possibly due to small sample sizes,” researcher Zhe Chen, PhD, of Biogen, and colleagues noted in their poster presentation.
Salynn Boyles, Contributing Writer, BreakingMED™
No funding source was reported for the cortical lesion study and GM Schiavi and other researchers reported no relevant disclosures.
The MRI study was supported by Novartis Pharma AG. G. Giovanonni reported receiving compensation from Abbvie, Atara Bio, Biogen, Sanofi-Genzyme, Merck KGaA, Novartis, Roche, Actelion, Celgene, Roche, Medscape, Oxford Health Policy Forum, Neurology Academy, Peervoice, Elsevier, and Bristows. Other researchers are employees of Novartis.
The ASCEND study was funded by Biogen Inc and the researchers are employees and/or hold stock or stock options in the company.
Cat ID: 130
Topic ID: 82,130,730,130,36,709,192,925,708
