Abstract Details

Title Reversal of the Pharmacodynamic Effects of Daclizumab HYP Following Treatment Washout: Results from the SELECTION Study

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 188

Objective

Background BACKGROUND: DAC HYP treatment is associated with expansion of CD56bright NK cells and reductions in FoxP3-positive T-regulatory (FoxP3+-Tregs) cells. SELECTION was a 52-week, randomized, double-blind study to evaluate the effect of extended treatment with DAC HYP, as well as a 24-week washout.

Design/Methods DESIGN/METHODS: Patients who received 150mg or 300mg DAC HYP in SELECT were randomized to continue their current dose or to a 24-week washout. CD56bright NK cells were defined as CD3-CD16+CD56bright lymphocytes and FoxP3+-Treg cells as CD4+CD127lowFoxP3+ T-cells using validated FACS assays. Cell counts were measured over the 24-week washout period in available samples.

Results RESULTS: Mean (SD) CD56bright counts were 8.7 (4.9) and 9.5 (5.9) at pretreatment baseline in DAC HYP 150mg- and 300mg-washout groups, respectively, increased after 52 weeks of DAC HYP treatment (mean [SD] change from baseline [CFB]: 150mg: 43.1 [36.9]; 300mg: 54.1 [60.6]), and returned to baseline during washout (mean [SD] CFB: 150mg: 2.0 [6.1]; 300mg: 1.2 [8.0]). Mean (SD) FoxP3+-Treg counts were 14.6 (9.9) and 12.2 (8.9) cells/mm3 at pretreatment baseline in DAC HYP 150mg- and 300mg-washout groups, respectively, decreased after 52 weeks of DAC HYP (mean [SD] CFB: 150mg: -7.7 [9.7]; 300mg: -7.8 [8.8]), and returned to baseline during washout (mean [SD] CFB: 150mg: 0.5 [12.4]; 300mg: 1.4 [11.4]). Changes after the 24-week washout were comparable to those in placebo-treated patients (mean [SD] CFB: CD56bright, 0.2 [4.3]; FoxP3, 0.1 [10.2]). During washout, gadolinium-enhancing lesions were below pretreatment baseline, and the safety profile was similar to the treatment period.

Conclusions CONCLUSIONS: The pharmacodynamic effects of DAC HYP reversed to baseline levels over 6 months of washout in RRMS patients. During washout, rebound of disease activity was not apparent and there was no adverse impact on safety.

Authors/Disclosures
Devangi S. Mehta, PhD (Biogen) PRESENTER	No disclosure on file
Lakshmi S. Amaravadi, PhD (Sr. Director, Translational Medicine)	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.
James Sheridan, PhD (Abbott Labs)	No disclosure on file
Katherine A. Riester, MPH (Biogen)	No disclosure on file
Richard A. Macdonell, MD, FAAN (Austin Health)	Dr. Macdonell has nothing to disclose.
	No disclosure on file
Gavin Giovannoni, MD (QMUL)	Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche-Genentech. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astoria Biologica. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas. Dr. Giovannoni 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. Giovannoni 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. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape.
Jacob S. Elkins, MD	No disclosure on file

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