Abstract Details

Title Regulatory T-Cell Numbers in Patients with Relapsing-Remitting MS Were Not Associated with Clinical or MRI Outcomes in the SELECT Study

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 192

Objective

Background BACKGROUND: Daclizumab is a humanized monoclonal antibody that targets activated immune cells by blocking interleukin-2 (IL-2) interaction with the alpha subunit (CD25) of the human IL-2 receptor. Tregs abundantly express CD25 and are mediators of immune tolerance, but their role in RRMS is unclear.

Design/Methods DESIGN/METHODS: SELECT was a randomized, double-blind, placebo-controlled study of subcutaneous DAC HYP 150mg, 300mg or placebo every 4 weeks for 52 weeks in patients with RRMS. Putative Tregs were defined as CD4+CD127lowFoxP3+ T-cells by fluorescence-activated cell sorting assay at baseline and 7 post-baseline time points. Associations between Treg counts and clinical/MRI outcomes were examined in placebo-treated (n=179) and pooled DAC HYP- treated (n=370) patients.

Results RESULTS: Treg counts in placebo-treated patients remained stable throughout the study (mean [standard deviation] of ln[Treg counts], minimum: 2.18 [0.79]; maximum: 2.41 [0.64]) and in the DAC HYP group they declined from baseline to Week 8 (P<0.001) and then remained stable to Week 52 (baseline: 2.37 [0.72]; Week 8: 1.36 [0.83]; Week 52: 1.43 [0.76]). Baseline Treg counts in placebo-treated patients were not predictive of: new/enlarging T2 lesions at Week 24 (P=0.936) or Week 52 (P=0.286), annualized relapse rate (ARR; P=0.201), or relapse-free status (P=0.618). In DAC HYP-treated patients, there was no association between end of treatment Treg counts and new/enlarging T2 lesions at Week 52 (P=0.66) or ARR (P=0.57) or the incidence of infections (P?0.190), cutaneous events (P?0.253), or liver function test abnormalities (P?0.496) at baseline, Week 16 or Week 52.

Conclusions CONCLUSIONS: Treg counts were reduced during DAC HYP treatment but were not detectably associated with clinical/MRI outcomes or adverse events in DAC HYP-treated patients.

Authors/Disclosures
PRESENTER	No disclosure on file
Ralf Gold, MD (Neurologische Universitaetsklinik)	Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen . Dr. Gold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer Vital. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharamaceuticals. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishers. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Novartis. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Biogen. The institution of Dr. Gold has received research support from Novartis. The institution of Dr. Gold has received research support from Biogen.
Xiaojun You, PhD (Biogen Idec Inc.)	No disclosure on file
James Sheridan, PhD (Abbott Labs)	No disclosure on file
Alessia Di Sapio	Alessia Di Sapio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Alessia Di Sapio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion . Alessia Di Sapio has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck. Alessia Di Sapio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Alessia Di Sapio has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Sanofi . The institution of Alessia Di Sapio has received research support from Ministero della Salute. The institution of Alessia Di Sapio has received research support from Sanofi.
Lakshmi S. Amaravadi, PhD (Sr. Director, Translational Medicine)	No disclosure on file
	No disclosure on file
Jacob S. Elkins, MD	No disclosure on file

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