Abstract
BACKGROUND: To investigate the intrathecal effect of cladribine tablets on cerebrospinal fluid (CSF) inflammatory proteomic profile, cortical lesions (CLs), paramagnetic rim lesions (PRLs) number and cognition after 2 years of treatment. RESULTS: Forty-two patients with RRMS treated with cladribine tablets were enrolled in a prospective longitudinal 2-year study. All patients were scheduled to undergo a lumbar puncture before treatment initiation and after 2 years of treatment, a clinical evaluation, including Expanded Disability Status Scale (EDSS) assessment, every 6 months, and a 3T MRI every year. White matter lesion number and volume, CLs, PRLs number and neuropsychological status were evaluated. CSF levels of 17 inflammatory markers were assessed by multiplex immune assay. No evidence of disease activity (NEDA) was defined as the absence of relapses, MRI activity and 6-months confirmed disability progression, defined as an increase of ≥ 1 point in the EDSS. Thirty-nine patients completed the study, and 33 agreed to repeat the lumbar puncture. After two years, 23 (59%) patients retained the NEDA status. Cladribine tablets reduced most of the inflammatory markers in the CSF of patients, with a significant reduction, after correction for multiple comparisons, in levels of sTNFR1, Pentraxin3 and CCL22. No patients accumulated new CLs, and no significant changes in PRLs and cognition were observed over the follow-up. CONCLUSIONS: Cladribine tablets administration led to a reduction of intrathecal inflammatory markers. These findings, along with the absence of CLs and PRLs accumulation, suggest a potential effect of the drug on intrathecal compartmentalized inflammation.