To investigate effect of Cladribine on cerebrospinal fluid (CSF) inflammatory proteomic profile, cortical lesions (CLs) and positive RIM lesions (PRLs) in patients with relapsing-remitting MS (RRMS).

Cladribine is an oral drug capable to cross the blood-brain barrier and licensed for  treatment of relapsing MS. Its efficacy on intrathecal inflammatory markers and MRI markers of chronic compartmentalized inflammation remains unclear.

Thirty-nine patients completed the study. Baseline median EDSS was 2(0-5), disease duration was 2.4±4.3 years. After two years, 19 (48.7%) patients retained the NEDA status. Cladribine reduced most of CSF markers. After correction for multiple comparisons, a reduction of TNF (p=0.047), TNFR1 (p=0.039), Pentraxin3 (p=0.002) and CCL22 (p=0.017) and a almost significant reduction of CCL21, CXCL5, IFNgamma, BAFF, CD163, Chitinase 3like1 were detected. On the contrary, CXCL12, OPN, sTNFR2 didn’t decrease after treatment. The decrease in markers was more pronounced in those patients that reached NEDA status. The down-regulation of TWEAK and CXCL13 correlated with EDSS change (r=0.34,p=0.034 and r=0.32,p=0.043, respectively). No patients accumulated new CLs neither a significant increase in PRLs was observed.