Reversible effects of daclizumab HYP on lymphocyte counts in RRMS patients: Data from the SELECT trilogy studies

Objective: Evaluate effects of daclizumab HYP 150mg on total and differential lymphocyte populations in relapsing-remitting multiple sclerosis patients. Background: Daclizumab HYP selectively modulates interleukin-2 receptor signaling, leading to inhibitory effects on pro-inflammatory effector T-cell activities and increased immunoregulatory CD56 bright natural killer (NK) cell numbers. Methods: Total and differential lymphocyte counts (CD56 bright NK cells, regulatory T-cells [Tregs] and CD4 + and CD8 + T-cells) were assessed using validated flow cytometry assays in patients who received daclizumab HYP 150mg in SELECT and SELECTION of the SELECT Trilogy. Upon completion of SELECT and enrollment in SELECTION, patients were randomized to continue daclizumab HYP treatment or to a 24-week washout period followed by reinitiation of daclizumab HYP 150mg (continued in SELECTED). Results: Seventy-three patients who received daclizumab HYP 150mg in SELECT were randomized to a 24-week washout period and completed treatment in By week 52 of SELECT, mean CD56 bright NK counts expanded by ~5-fold and median Tregs declined by 58.4[percnt] from baseline. Small decreases were observed in mean CD4 + and CD8 + T-cell counts from baseline (−4.1[percnt] and −4.5[percnt], respectively). At the end of the washout period (Week 20 of SELECTION), mean CD56 bright NK, Tregs, CD4 + and CD8 + cell counts returned to SELECT baseline values. Over SELECT and SELECTION, the mean ratio of CD4 + to CD8 + remained stable (range: 2.0-2.3). Mean changes in total lymphocyte counts observed during SELECT were also reversed by end of washout in SELECTION. Conclusions: These data extend previous observations on the rapid pharmacodynamic effects of daclizumab HYP on CD56 bright NK cells and Tregs at treatment initiation and provide additional evidence for an immunomodulatory effect of daclizumab HYP based on absence of profound cell depletion during treatment and modest decreases in lymphocyte counts that are reversible upon treatment discontinuation. Study Supported by: Biogen and AbbVie Biotherapeutics Inc. Disclosure: Dr. Fam has received personal compensation for activities with Biogen Idec as an employee. Dr. Mokliatchouk has received personal compensation from Biogen Idec as an employee. Dr. Mehta has received personal compensation for activities with Biogen as an employee. Dr. Riester holds stock and/or stock options in Biogen Idec, which sponsored research which Dr. Riester was involved as an investigator. Dr. Sheridan has received personal compensation for activities with AbbVie as an employee. Dr. McCroskery has received personal compensation for activities with Biogen as an employee. Dr. McCroskery holds stock and/or stock options in Biogen, which supported research in which Dr. McCroskery was involved as an investigator. Dr. Elkins holds stock and/or stock options in Biogen, which sponsored research in which Dr. Elkins was involved as a researcher. Dr. Amaravadi has received personal compensation for activities with Biogen as an employee.