MRI and laboratory monitoring of disease-modifying therapy efficacy and risks

Abstract

Purpose of reviewIncreasingly, therapeutic strategy in multiple sclerosis (MS) is informed by imaging and laboratory biomarkers, in addition to traditional clinical factors. Here, we review aspects of monitoring the efficacy and risks of disease-modifying therapy (DMT) with both conventional and emerging MRI and laboratory measures.Recent findingsThe adoption of consensus-driven, stable MRI acquisition protocols and artificial intelligence-based, quantitative image analysis is heralding an era of precision monitoring of DMT efficacy. New MRI measures of compartmentalized inflammation, neuro-degeneration and repair complement traditional metrics but require validation before use in individual patients. Laboratory markers of brain cellular injury, such as neurofilament light, are robust outcomes in DMT efficacy trials; their use in clinical practice is being refined. DMT-specific laboratory monitoring for safety is critical and may include lymphocytes, immunoglobulins, autoimmunity surveillance, John Cunningham virus serology and COVID-19 vaccination seroresponse.SummaryA biomarker-enhanced monitoring strategy has immediate clinical application, with growing evidence of long-term reductions in disability accrual when both clinically symptomatic and asymptomatic inflammatory activity is fully suppressed; and amelioration of the risks associated with therapy. Emerging MRI and blood-based measures will also become important tools for monitoring agents that target the innate immune system and promote neuro-repair.

Ai-Based Mri Monitoring in Multiple Sclerosis: Real-World Clinical Validation

“…The detection of clinically silent new MRI lesions is an important determinant of treatment strategy [4] that may, in its own right, lead to escalation of immunotherapy. Most modern therapeutic paradigms target No Evidence of Disease Activity (NEDA) [7], which encompasses both clinical and radiological disease quiescence.…”

“…Inflammatory activity, the pathological substrate for RAW, and response to DMT are monitored by regular clinical assessment and repeated magnetic resonance imaging (MRI), usually on an annual basis [4]. MRI is also the most important tool for neurologists to assess disease activity that does not manifest with overt clinical change, but potentially injures vast numbers of axons and disrupting complex integrated brain networks.…”

“…MRI is also the most important tool for neurologists to assess disease activity that does not manifest with overt clinical change, but potentially injures vast numbers of axons and disrupting complex integrated brain networks. Specifically, the development of new or enlarging hyperintensities on FLAIR MRI and/or new contrast enhancing lesions (CELs) on T1-w MRI generally suggests inadequate suppression of inflammatory activity and may prompt the clinician to change the patient's DMT [4]. PIRA is more difficult to characterise by MRI, but at the group level disability worsening correlates well with whole brain volume change [5,6].…”

“…Similarly, longitudinal change in brain volume during the typical 12-month interval between MRI scans is usually small and not detectable by visual inspection. While short-term changes in brain volume are difficult to interpret in individual patients, a consistent adverse trajectory over multiple clinical epochs or more severe brain atrophy (>0.8% percent BVL per annum) over a single epoch, may influence or support clinical decisions to escalate or switch DMT [4].…”

Editorial: Advances in Multiple Sclerosis

“…To tailor therapies to an individual person with MS judicious use of this arsenal is of paramount importance and requires an assessment of risks, repeated monitoring of efficacy and safety. How MRI and laboratory surveillance aids in this process to achieve an optimal benefit risk balance and outcome is reviewed in light of new observations by Barnett et al [16].…”