Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets: A MAGNIFY-MS Substudy
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Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets : A MAGNIFY-MS Substudy. / Wiendl, Heinz; Schmierer, Klaus; Hodgkinson, Suzanne; Derfuss, Tobias; Chan, Andrew; Sellebjerg, Finn; Achiron, Anat; Montalban, Xavier; Prat, Alexandre; De Stefano, Nicola; Barkhof, Frederik; Leocani, Letizia; Vermersch, Patrick; Chudecka, Anita; Mwape, Claire; Holmberg, Kristina H.; Boschert, Ursula; Roy, Sanjeev.
In: Neurology: Neuroimmunology & Neuroinflammation, Vol. 10, No. 1, e200048, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets
T2 - A MAGNIFY-MS Substudy
AU - Wiendl, Heinz
AU - Schmierer, Klaus
AU - Hodgkinson, Suzanne
AU - Derfuss, Tobias
AU - Chan, Andrew
AU - Sellebjerg, Finn
AU - Achiron, Anat
AU - Montalban, Xavier
AU - Prat, Alexandre
AU - De Stefano, Nicola
AU - Barkhof, Frederik
AU - Leocani, Letizia
AU - Vermersch, Patrick
AU - Chudecka, Anita
AU - Mwape, Claire
AU - Holmberg, Kristina H.
AU - Boschert, Ursula
AU - Roy, Sanjeev
N1 - Publisher Copyright: © American Academy of Neurology.
PY - 2023
Y1 - 2023
N2 - Background and ObjectivesCladribine 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).MethodsImmunophenotyping 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.ResultsThe 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.DiscussionCladribine 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 InformationClinicalTrials.gov Identifier: NCT03364036. Date registered: December 06, 2017.
AB - Background and ObjectivesCladribine 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).MethodsImmunophenotyping 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.ResultsThe 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.DiscussionCladribine 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 InformationClinicalTrials.gov Identifier: NCT03364036. Date registered: December 06, 2017.
U2 - 10.1212/NXI.0000000000200048
DO - 10.1212/NXI.0000000000200048
M3 - Journal article
C2 - 36411081
AN - SCOPUS:85142363165
VL - 10
JO - Neurology: Neuroimmunology & Neuroinflammation
JF - Neurology: Neuroimmunology & Neuroinflammation
SN - 2332-7812
IS - 1
M1 - e200048
ER -
ID: 367306457