RT Journal Article
SR Electronic
T1 Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e200048
DO 10.1212/NXI.0000000000200048
VO 10
IS 1
A1 Heinz Wiendl
A1 Klaus Schmierer
A1 Suzanne Hodgkinson
A1 Tobias Derfuss
A1 Andrew Chan
A1 Finn Sellebjerg
A1 Anat Achiron
A1 Xavier Montalban
A1 Alexandre Prat
A1 Nicola De Stefano
A1 Frederik Barkhof
A1 Letizia Leocani
A1 Patrick Vermersch
A1 Anita Chudecka
A1 Claire Mwape
A1 Kristina H. Holmberg
A1 Ursula Boschert
A1 Sanjeev Roy
YR 2023
UL http://nn.neurology.org/content/10/1/e200048.abstract
AB Background and Objectives Cladribine tablets cause a reduction in lymphocytes with a predominant effect on B-cell and T-cell counts. The MAGNIFY-MS substudy reports the dynamic changes on multiple peripheral blood mononuclear cell (PBMC) subtypes and immunoglobulin (Ig) levels over 12 months after the first course of cladribine tablets in patients with highly active relapsing multiple sclerosis (MS).Methods Immunophenotyping was performed at baseline (predose) and at the end of months 1, 2, 3, 6, and 12 after initiating treatment with cladribine tablets. Assessments included lymphocyte subtype counts of CD19+ B cells, CD4+ and CD8+ T cells, CD16+ natural killer cells, plasmablasts, and Igs. Immune cell subtypes were analyzed by flow cytometry, and serum IgG and IgM were analyzed by nephelometric assay. Absolute cell counts and percentage change from baseline were assessed.Results The full analysis set included 57 patients. Rapid reductions in median CD19+, CD20+, memory, activated, and naive B-cell counts were detected, reaching nadir by month 2. Thereafter, total CD19+, CD20+, and naive B-cell counts subsequently reconstituted, but memory B cells remained reduced by 93%–87% for the remainder of the study. The decrease in plasmablasts was slower, reaching nadir at month 3. Decrease in T-cell subtypes was also slower and more moderate compared with B-cell subtypes, reaching nadir between months 3 and 6. IgG and IgM levels remained within the normal range over the 12-month study period.Discussion Cladribine tablets induce a specific pattern of early and sustained PBMC subtype dynamics in the absence of relevant Ig changes: While total B cells were reduced dramatically, T cells were affected significantly less. Naive B cells recovered toward baseline, naive CD4 and CD8 T cells did not, and memory B cells remained reduced. The results help to explain the unique immune depletion and repopulation architecture regarding onset of action and durability of effects of cladribine tablets while largely maintaining immune competence.Trial Registration Information ClinicalTrials.gov Identifier: NCT03364036. Date registered: December 06, 2017.DMTs=disease-modifying therapies; EDSS=Expanded Disability Status Scale; Ig=immunoglobulin; MS=multiple sclerosis; NK=natural killer; PBMC=peripheral blood mononuclear cell; TEMRA=terminally differentiated effector memory RA+; Th=T helper; Treg=T regulatory