Bagnato F, Mordin M, Greene N, Mahida S, Higuchi K, van Wingerden J. Evaluating association of chronic active lesions with disability in multiple sclerosis: a systematic literature review. Poster presented at the Academy of Managed Care Pharmacy (AMCP) Nexus 2024; October 14, 2024. Las Vegas, NV. [abstract] J Manag Care Spec Pharm. 2024 Oct; 30(10-c):S155. Previously presented at the 10th Congress of the European Academy of Neurology.

INTRODUCTION:  Multiple Sclerosis (MS) is characterized by a complex interplay of acute and chronic inflammation as well as myelin and axonal damage. Improvements in magnetic resonance imaging (MRI) have expanded our understanding of MS evolution in vivo and facilitated the detection of inflammatory lesions, particularly chronic active lesions (CALs). Currently, there are three in vivo biomarkers of CALs; paramagnetic rim lesions (PRLs), the MRI-defined slowly expanding lesions (SELs), and 18kDa translocator protein (TSPO) positron emission tomography (PET) rim-positive lesions.

OBJECTIVE: This literature review evaluated the association between CALs (measured as either PRLs or MRI-defined SELs) and measures of disease progression and worsening disability in people with MS (pwMS).

METHODS:  A systematic literature search was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, and Cochrane Library on April 21, 2023. The review included studies assessing associations between CAL and clinical/radiological outcome of disability accumulation in people with any MS phenotype.

RESULTS: A total of 149 unique studies were identified and 30 met the inclusion criteria. Of these, 18 evaluated PRLs, 9 evaluated MRI-defined SELs, 1 evaluated both, and 2 evaluated TSPO-positive lesions. The presence of PRLs was associated with disability worsening in 17 studies, with 9 of those studies reporting a positive association between the number or volume of PRLs and disability worsening. MRI-defined SELs were associated with disability worsening in 10 studies.

CONCLUSION: This literature review found a clear association between worsening disability in MS and the presence of CALs, both PRLs and SELs. Despite several obstacles that remain to be addressed before CALs can be adopted into routine clinical practice, establishing a CAL imaging biomarker that accurately predicts disease progression and worsening disability is certainly a necessity to evaluate (para)clinical manifestations of smoldering neuroinflammation to optimize personalized MS treatment and management.