CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis

Area of Science:

• Neuroimmunology
• Biomarker Discovery
• Multiple Sclerosis Therapeutics

Background:

• Cladribine is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS).
• Early disease activity can occur within the first year of cladribine treatment.
• Predictive biomarkers for early disease activity are needed to optimize patient management.

Purpose of the Study:

• To identify cerebrospinal fluid (CSF) markers associated with clinical and radiological responses to cladribine in RRMS patients.
• To evaluate the prognostic value of CSF biomarkers for predicting disease activity post-cladribine initiation.

Main Methods:

• A prospective longitudinal study included 42 RRMS patients treated with cladribine.
• CSF samples were collected at treatment initiation for analysis of 67 inflammatory markers.
• Clinical and 3T MRI assessments (including white matter and cortical lesions) were performed at 6, 12, and 24 months.
• No evidence of disease activity (NEDA-3) status was assessed at two years.

Main Results:

• 48% of patients achieved NEDA-3 status at two years.
• Several CSF markers, including Chitinase 3-like 1, were associated with disease activity.
• Elevated Chitinase 3-like 1 levels significantly predicted disease activity (p = 0.049) in a multivariate model.
• Chitinase 3-like 1 improved the prediction of disease activity when combined with clinical and MRI data (AUC = 0.76).

Conclusions:

• CSF Chitinase 3-like 1 shows potential as a prognostic biomarker for predicting early disease activity in cladribine-treated RRMS patients.
• Further research is warranted to explore the drug's impact on macrophage and microglia activation.
• This finding may aid in tailoring cladribine therapy for individual RRMS patients.