‘Hidden’ Signs May Signal Subclinical Progression in Early MS

Focusing solely on relapse rates and magnetic resonance imaging (MRI) lesion activity to track disease progression in patients with early multiple sclerosis (MS) may miss indicators of subclinical disease activity, with important implications for patients, according to an article in the Journal of Neurology.

“A greater awareness of ‘hidden’ indicators, potentially combined with biomarkers to reveal silent disease activity and neurodegeneration underlying MS, would provide a more complete picture of MS and allow for timely therapeutic intervention with high-efficacy therapies or switching disease-modifying therapies to address suboptimal treatment responses,” wrote corresponding author Daniel Ontaneda, MD, PhD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, Cleveland, Ohio, and article coauthors.

The review article outlines several early indicators of disease activity not reflected in relapses and MRI lesions that, according to the authors, should factor into the management of patients with confirmed early MS. Among them are cognitive impairment, fatigue, anxiety, depression, migraine/headache, and sleep disorders.

Additionally, elevations of certain molecules in the blood or cerebral spinal fluid of patients show potential for use as prognostic biomarkers. Although research is still in the investigational stage, they include oligoclonal bands of immunoglobulin G, neurofilament light, and several other possibilities.

As more data on hidden indicators of MS emerges, consensus guidelines will need to consider earlier use of high-efficacy therapies, the article advises.

“Early detection of MS allows early treatment initiation,” the authors wrote. “In light of emerging evidence and pending outcomes of ongoing clinical trials, early high-efficacy therapy is appropriate and can be considered not only in cases of severe disease activity. Long-term safety data and clinical trial data on early high-efficacy therapies are needed to help give physicians and payers confidence in its use.”

Reference

Ontaneda D, Chitnis T, Rammohan K, Obeidat AZ. Identification and management of subclinical disease activity in early multiple sclerosis: a review. J Neurol. 2024;271(4):1497-1514. doi: 10.1007/s00415-023-12021-5