Effects of cladribine tablets on lymphocyte subsets in patients with multiple sclerosis: an extended analysis of surface markers

Olaf Stuve, Per Soelberg Soerensen, Thomas Leist, Gavin Giovannoni, Yann Hyvert, Doris Damian, Fernando Dangond, Ursula Boschert

Research output: Contribution to journalArticle

Abstract

Background: Cladribine tablets 3.5 mg/kg cumulative over 2 years (CT3.5) had significant clinical/imaging effects in patients with clinically isolated syndrome (CIS; ORACLE-MS) or relapsing-remitting MS (RRMS; CLARITY and CLARITY Extension). This analysis compared the effect of cladribine tablets on the dynamics of immune cell reduction and reconstitution in ORACLE-MS, CLARITY, and CLARITY Extension during the first year of treatment (i.e. the first course of CT1.75) in patients randomized to CT3.5. Methods: Lymphocyte subtypes were analyzed using multiparameter flow cytometry. Changes in cell counts and relative proportions of lymphocytes were evaluated at weeks 5, 13, 24, and 48. Results: Across studies, consistent and comparable selective kinetics of immune cell populations occurred following the first treatment year with CT. A rapid reduction in CD16+/CD56+ cells (week 5 nadir), a more marked reduction in CD19+ B cells (week 13 nadir), and a less-pronounced effect on CD4+ (week 13 nadir) and CD8+ T cells (week 24 nadir) was shown. There was little effect on neutrophils or monocytes. Lymphocyte recovery began after treatment with CT3.5. Regarding relative proportions of naïve and memory T-cell subtypes in ORACLE-MS, the proportion of naïve-like naturally occurring T-regulatory cells (nTregs) decreased, and the proportion of memory-like nTregs increased, relative to total CD4+ T cells. Conclusions: CT3.5 has comparable effects on the immune systems of patients with CIS or RRMS. The pronounced reduction and recovery dynamics of CD19+ B cells and relative changes in the proportion of some immune cell subtypes may underlie the clinical effects of CT3.5.

Original languageEnglish (US)
JournalTherapeutic Advances in Neurological Disorders
Volume12
DOIs
StatePublished - Jun 1 2019

Fingerprint

Cladribine
Lymphocyte Subsets
Tablets
Multiple Sclerosis
Lymphocytes
T-Lymphocytes
B-Lymphocytes
Regulatory T-Lymphocytes
Monocytes
Immune System
Flow Cytometry
Neutrophils
Therapeutics
Cell Count
Population

Keywords

  • cladribine tablets
  • CLARITY
  • CLARITY Extension
  • lymphocytes
  • multiple sclerosis
  • ORACLE-MS
  • subsets

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology

Cite this

Effects of cladribine tablets on lymphocyte subsets in patients with multiple sclerosis : an extended analysis of surface markers. / Stuve, Olaf; Soelberg Soerensen, Per; Leist, Thomas; Giovannoni, Gavin; Hyvert, Yann; Damian, Doris; Dangond, Fernando; Boschert, Ursula.

In: Therapeutic Advances in Neurological Disorders, Vol. 12, 01.06.2019.

Research output: Contribution to journalArticle

Stuve, Olaf ; Soelberg Soerensen, Per ; Leist, Thomas ; Giovannoni, Gavin ; Hyvert, Yann ; Damian, Doris ; Dangond, Fernando ; Boschert, Ursula. / Effects of cladribine tablets on lymphocyte subsets in patients with multiple sclerosis : an extended analysis of surface markers. In: Therapeutic Advances in Neurological Disorders. 2019 ; Vol. 12.
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abstract = "Background: Cladribine tablets 3.5 mg/kg cumulative over 2 years (CT3.5) had significant clinical/imaging effects in patients with clinically isolated syndrome (CIS; ORACLE-MS) or relapsing-remitting MS (RRMS; CLARITY and CLARITY Extension). This analysis compared the effect of cladribine tablets on the dynamics of immune cell reduction and reconstitution in ORACLE-MS, CLARITY, and CLARITY Extension during the first year of treatment (i.e. the first course of CT1.75) in patients randomized to CT3.5. Methods: Lymphocyte subtypes were analyzed using multiparameter flow cytometry. Changes in cell counts and relative proportions of lymphocytes were evaluated at weeks 5, 13, 24, and 48. Results: Across studies, consistent and comparable selective kinetics of immune cell populations occurred following the first treatment year with CT. A rapid reduction in CD16+/CD56+ cells (week 5 nadir), a more marked reduction in CD19+ B cells (week 13 nadir), and a less-pronounced effect on CD4+ (week 13 nadir) and CD8+ T cells (week 24 nadir) was shown. There was little effect on neutrophils or monocytes. Lymphocyte recovery began after treatment with CT3.5. Regarding relative proportions of na{\"i}ve and memory T-cell subtypes in ORACLE-MS, the proportion of na{\"i}ve-like naturally occurring T-regulatory cells (nTregs) decreased, and the proportion of memory-like nTregs increased, relative to total CD4+ T cells. Conclusions: CT3.5 has comparable effects on the immune systems of patients with CIS or RRMS. The pronounced reduction and recovery dynamics of CD19+ B cells and relative changes in the proportion of some immune cell subtypes may underlie the clinical effects of CT3.5.",
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T2 - an extended analysis of surface markers

AU - Stuve, Olaf

AU - Soelberg Soerensen, Per

AU - Leist, Thomas

AU - Giovannoni, Gavin

AU - Hyvert, Yann

AU - Damian, Doris

AU - Dangond, Fernando

AU - Boschert, Ursula

PY - 2019/6/1

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AB - Background: Cladribine tablets 3.5 mg/kg cumulative over 2 years (CT3.5) had significant clinical/imaging effects in patients with clinically isolated syndrome (CIS; ORACLE-MS) or relapsing-remitting MS (RRMS; CLARITY and CLARITY Extension). This analysis compared the effect of cladribine tablets on the dynamics of immune cell reduction and reconstitution in ORACLE-MS, CLARITY, and CLARITY Extension during the first year of treatment (i.e. the first course of CT1.75) in patients randomized to CT3.5. Methods: Lymphocyte subtypes were analyzed using multiparameter flow cytometry. Changes in cell counts and relative proportions of lymphocytes were evaluated at weeks 5, 13, 24, and 48. Results: Across studies, consistent and comparable selective kinetics of immune cell populations occurred following the first treatment year with CT. A rapid reduction in CD16+/CD56+ cells (week 5 nadir), a more marked reduction in CD19+ B cells (week 13 nadir), and a less-pronounced effect on CD4+ (week 13 nadir) and CD8+ T cells (week 24 nadir) was shown. There was little effect on neutrophils or monocytes. Lymphocyte recovery began after treatment with CT3.5. Regarding relative proportions of naïve and memory T-cell subtypes in ORACLE-MS, the proportion of naïve-like naturally occurring T-regulatory cells (nTregs) decreased, and the proportion of memory-like nTregs increased, relative to total CD4+ T cells. Conclusions: CT3.5 has comparable effects on the immune systems of patients with CIS or RRMS. The pronounced reduction and recovery dynamics of CD19+ B cells and relative changes in the proportion of some immune cell subtypes may underlie the clinical effects of CT3.5.

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