PT  - JOURNAL ARTICLE
AU  - Heinz Wiendl
AU  - Klaus Schmierer
AU  - Suzanne Hodgkinson
AU  - Tobias Derfuss
AU  - Andrew Chan
AU  - Finn Sellebjerg
AU  - Anat Achiron
AU  - Xavier Montalban
AU  - Alexandre Prat
AU  - Nicola De Stefano
AU  - Frederik Barkhof
AU  - Letizia Leocani
AU  - Patrick Vermersch
AU  - Anita Chudecka
AU  - Claire Mwape
AU  - Kristina H. Holmberg
AU  - Ursula Boschert
AU  - Sanjeev Roy
TI  - Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets
AID  - 10.1212/NXI.0000000000200048
DP  - 2023 Jan 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e200048
VI  - 10
IP  - 1
4099  - http://nn.neurology.org/content/10/1/e200048.short
4100  - http://nn.neurology.org/content/10/1/e200048.full
SO  - Neurol Neuroimmunol Neuroinflamm2023 Jan 01; 10
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