Regulatory T-Cell Numbers in Patients with Relapsing-Remitting MS Were Not Associated with Clinical or MRI Outcomes in the SELECT Study (P05.192)

OBJECTIVE: To examine the relationship between putative regulatory T cell (Treg) counts and outcomes in relapsing-remitting MS (RRMS) patients treated with monthly subcutaneous daclizumab high-yield process (DAC HYP) or placebo. 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: 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: 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 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. Supported by: Biogen Idec and Abbott Biotherapeutics. Disclosure: Dr. Selmaj has received personal compensation for activities with Biogen Idec, Genzyme, Ono Pharmaceutical, Novartis, Bayer, Hoffmann LaRoche, Merck, Serono and Synthon. Dr. Gold has received personal compensation for activities with Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Disorders. Dr. Gold has received a license fee from Biogen Idec. Dr. Gold has received research support from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. You has received personal compensation for activities with Biogen Idec. Dr Sheridan has received personal compensation for activities with Abbott Biotherapeutics as an employee. Dr. Sheridan holds stock and/or stock options in Abbott Biotherapeutics. Dr. Amaravadi has received personal compensation for activities with Biogen Idec as an employee. Dr. Amaravadi holds stock and/or stock options in Biogen Idec. Dr. Amaravadi has received research support from Biogen Idec. Dr. Fontenot has received personal compensation for activities with Biogen Idec as an employee. Dr. Fontenot has received research support from Biogen Idec. Dr. Elkins has received personal compensation for activities with Biogen Idec as an employee. Dr. Elkins holds stock and/or stock options in Biogen Idec.