To study the impact of cladribine tablets (CladT) on B cell function: kappa and lambda free light chain levels (K/L-FLC), immunoglobulin (Ig) G production including B-cell chemoattractant CXCL-13.

Multiple sclerosis (MS) is associated with an intrathecal oligoclonal IgG response. In the chronic progressive cladribine trial, patients treated with CladT had a significant decline in the number of oligoclonal bands. Recently, K-FLC also secreted by B cells, alongside intact immunoglobulins, have emerged as a new quantitative biomarker of intrathecal antibody production. We therefore designed a prospective study to see if the sustained depletion of memory B cells with CladT parallels an intrathecal effect on their biological activity.

CladB study (IRAS 262436) is a 96-week prospective longitudinal biomarker study examining the effects of CladT in RRMS. Paired cerebrospinal fluid (CSF)/blood were taken at baseline (predosing), 48 and 96 weeks after initiating treatment. K/L-FLC, Ig and albumin levels (for index calculation) were assayed using an Optilite turbidimeter (The Binding Site). Chemokine CXCL-13 were assayed using immunoassay from Mesoscale Discovery.

Ten participants (3 male, 7 female, mean age 35.9 ± 10.5 (SD) and EDSS 2.5 (range 0-6) at baseline were enrolled in the study and completed the 96-weeks assessment. K-FLC index reduced from mean 164.5 ± 227.1 (SD) at baseline to 71.3 ± 84.7 at W48 (p=0.002) and 64.4 ± 67.3 at W96 (p=0.01). This coincided with reductions in IgG index (1.1 ± 0.5 (SD) at baseline, 0.8 ± 0.4 (p=0.014) at 48W and 0.8 ± 0.3 (P=0.02) at 96W and CSF CXCL-13 88.6± 68.4 (SD) pg/ml, 39.4 ± 35.2 mg/ml (p=0.037) at 48W and 19.1 ± 11.7pg/ml at 96W (p=0.027). L-FLC were unaffected.

CladT had sustained effects on intrathecal antibody production at 96W, mirroring lowering in total intrathecal IgG and B-cell chemoattractant CXCL-13 production in the CSF.