MSDA Test Identified as Biomarker-Based Instrument to Assess Disease Activity in Multiple Sclerosis

The Multiple Sclerosis Disease Activity (MSDA) test can assist in monitoring therapeutic response to glatiramer acetate (GA) and biologic agents as a biomarker-based instrument for assessing disease activity in patients with multiple sclerosis (MS), a recent study found.¹

Data were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022, February 24-26, in West Palm Beach, Florida, with investigators concluding that the test could further aid in assessing clinically challenging situations, specifically when clinical measures are confounded by inflammatory or noninflammatory changes from pseudorelapses.

Led by AlexandruTatomir, MD, PhD, postdoctoral fellow, department of neurology, University of Maryland School of Medicine in Baltimore, Maryland; and intern, Centre HospitalierMétropoleSavoie, in Chambery, France, investigators utilized 6 markers to detect relapses and response to GA therapy and found a significant positive correlation between Expanded Disability Status Scale (EDSS) scores and MSDA scores (r = 0.5879; P = .0002). A total of 60 patients with relapsing remitting MS were included in the study who were also naïve to treatment with disease-modifying drugs.

Each marker was assigned a positive or negative value depending on levels obtained, which were then used to establish an MSDA score. Derived from receiver operating characteristic analysis, cutoff values for detecting relapses were less than 1.27 for RGC-32, less than 52.6 for FasL, greater than 16.9 for IL-21, less than 3.05 for SIRT1, less than 0.11 for phosphorylated

SIRT1 (p-SIRT1), and greater than 1.2 for JNK1, p54. Cutoff values for measuring response to GA therapy were less than 2.52 for RGC-32, less than 85.4 for FasL, greater than 11.9 for normalized IL-21, less than 4.33 for normalized SIRT1, less than 0.3 for p-SIRT1, and greater than 1.3 for JNK1 p54.

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Values were considered positive (each awarded +1 point) if they were below the cutoff for RGC-32, FasL, SIRT1, or p-SIRT1 or above the cutoff value for IL-21 or JNK1 p54, indicating the patient as having a relapse or not responding to therapy with GA. Comparably, values above the cutoff value for RGC-32, FasL, SIRT1, or p-SIRT1 and below the cutoff for IL-21 and JNK1 p54 were considered negative (each awarded –1 point), which indicated the patient was stable or responding to therapy with GA. A relapse or being unresponsive to treatment was indicated by a score of MS disease activity above +1, while a score below –1 indicated the patient was stable or responding to treatment.

“Quantitative and regular assessment of disease activity in multiple sclerosis (MS) is required to achieve treatment targets and optimize clinical outcomes,” Tatomir et al wrote. “To predict relapses and monitor treatment response, a measure of disease activity in MS should reflect the pathological processes resulting in brain tissue damage and functional disability.”

Patients initiated treatment with GA at study entry and were followed at the University of Maryland Hospital, with clinical disease activity and serum biomarker concentrations measured at baseline, as well as months 3, 6, 9, and 12, following start of treatment. At each visit, EDSS scores were measured, and mRNA or protein levels of RGC-32, FasL, IL-21, SIRT1, p-SIRT1 and JNK1 p54 were integrated to derive an MSDA score (between –6 and +6).

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REFERENCE
1. Tatomir A, Anselmo F, Boodhoo D, et al. Novel multibiomarker test to assess multiple sclerosis disease activity. Presented at 2022 ACTRIMS Forum; February 24-26; West Palm Beach, FL and Virtual. Poster P050.