WED 183 Cladribine tablets effects on t cell subsets in patients with early ms

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Abstract

Background

Because of the durable clinical effects of cladribine tablets 3.5 mg/kg (CT3.5) in patients with multiple sclerosis, the influence of treatment on cells with regulatory immune function is of interest.

Objective

Examine effects on central memory; effector memory; and naturally occurring regulatory (nTregs) CD4 +T cells after first administration of CT3.5 in ORACLE-MS.

Methods

Peripheral blood T-lymphocytes were immunophenotyped at baseline, and Weeks 5, 13, 24, 48 in CT3.5 treated patients (n=41). Absolute numbers and proportions of central memory (CD4+RO+CCR7+), effector memory (CD4+RO+CCR7-), Th1-type (CD4+CXCR3+), nTregs (CD4+CD25+CD127-), including naïve-like and memory-like nTregs were measured.

Results

Greatest median reductions in absolute numbers occurred at Week-13 for effector memory cells (−54%); Week-24 for central memory (−63%) and Th1-type cells (−51%); with similar/slightly increased levels at Week-48. There was ~5% reduction in proportion of central memory cells, but no change in proportions of effector memory and Th1-type cells. Absolute numbers of nTregs (−48%), naïve-like (−67%) and memory-like nTregs (−42%) decreased by Week-48. nTregs and naïve-like nTregs proportions were unchanged. Proportions of memory-like nTregs slightly increased up to 48 Weeks.

Conclusion

CT3.5 administration has a comparable effect on CD4+ T cell subpopulations, with no dramatic shifts in proportions.

Disclaimer

http://medpub-poster.merckgroup.com/ABN2018DISC_ORACLE.pdf

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