Identification and management of subclinical disease activity in early multiple sclerosis: a review

Abstract

Importance Early treatment initiation in multiple sclerosis (MS) is crucial in preventing irreversible neurological damage and disability progression. The current assessment of disease activity relies on relapse rates and magnetic resonance imaging (MRI) lesion activity, but inclusion of other early, often “hidden,” indicators of disease activity may describe a more comprehensive picture of MS. Observations Early indicators of MS disease activity other than relapses and MRI activity, such as cognitive impairment, brain atrophy, and fatigue, are not typically captured by routine disease monitoring. Furthermore, silent progression (neurological decline not clearly captured by standard methods) may occur undetected by relapse and MRI lesion activity monitoring. Consequently, patients considered to have no disease activity actually may have worsening disease, suggesting a need to revise MS management strategies with respect to timely initiation and escalation of disease-modifying therapy (DMT). Traditionally, first-line MS treatment starts with low- or moderate-efficacy therapies, before escalating to high-efficacy therapies (HETs) after evidence of breakthrough disease activity. However, multiple observational studies have shown that early initiation of HETs can prevent or reduce disability progression. Ongoing randomized clinical trials are comparing escalation and early HET approaches. Conclusions and relevance There is an urgent need to reassess how MS disease activity and worsening are measured. 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 HET or switching DMTs to address suboptimal treatment responses.

Advanced MRI Techniques: Diagnosis and Follow-Up of Multiple Sclerosis

“…While common MRI protocols typically encompass T1-weighted (T1w), T2-weighted (T2w), and FLAIR [ 30 ], sequences with enhanced sensitivity for CLs detection, such as magnetization-prepared 2 rapid acquisition with gradient echo (MP2RAGE) [ 31 , 32 ] and double inversion recovery (DIR) [ 33 , 34 ], are increasingly employed in clinical practice [ 35 ]. Accurate lesion identification is crucial for monitoring disease activity and assessing the effectiveness of DMTs [ 36 ]. The number of CLs changes according to the phase of the disease, as they are more prevalent in SPMS compared to CIS or RRMS [ 37 ], with an impact on disability and cognitive impairment, thereby being vital indicators of disease progression in MS patients [ 27 , 28 ].…”

Value contribution of blood-based neurofilament light chain as a biomarker in multiple sclerosis using multi-criteria decision analysis

“…MS is characterized by neurodegeneration caused by axonal injury, present from the early disease stages ( 5 , 6 ). Due to the high variability of MS, in which the disease can manifest very differently between individuals and over time in the same patient, clinical and radiological markers may not be specific or sensitive enough to capture the full range of changes in terms of inflammation and neurodegeneration ( 7 ). Assessment and quantification of inflammatory activity and neurodegeneration are essential to establish the severity of the disease, the long-term prognosis, the need for treatment, the treatment option and the individual response to the selected treatment, as well as the achievement of therapeutic goals ( 7 , 8 ).…”