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Abstract Details

Prospective Longitudinal Study of Cladribine Tablets (CLADB Study) Demonstrates Sustained Reduction in Kappa Free Light Chains in Relapsing Multiple Sclerosis (RRMS) at 96 Weeks
Multiple Sclerosis
P10 - Poster Session 10 (11:45 AM-12:45 PM)
6-008

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.

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.

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.

Authors/Disclosures
Sharmilee Gnanapavan, MB (Institute of Neurology)
PRESENTER
Dr. Gnanapavan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. The institution of Dr. Gnanapavan has received research support from NIHR.
Francesca Ammoscato No disclosure on file
Justyna Skonieczna No disclosure on file
Jonathan Bestwick No disclosure on file
David Holden No disclosure on file
Mohammad Aboulwafa No disclosure on file
Michael Andrews No disclosure on file
Benjamin Turner Benjamin Turner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Serono.
Monica Marta Monica Calado-Marta has nothing to disclose.
Klaus Schmierer, MD, PhD (The Blizard Institute, Centre for Neuroscience, Surgery & Trauma) Dr. Schmierer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AXDEV. Dr. Schmierer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MedScape. Dr. Schmierer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroDiem. Dr. Schmierer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurology Academy. Dr. Schmierer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck KGaA. Dr. Schmierer has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Merck KGaA. Dr. Schmierer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for F. Hoffmann-La Roche AG. Dr. Schmierer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Dr. Schmierer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva.
David Baker No disclosure on file
Gavin Giovannoni, MD (QMUL) Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Japanese Tobacco. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aurinia Pharmaceuticals. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Oxford Health Policy Forum. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Peervoice. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Bristows .