Therapeutic Advances in Neurological Disorders 2014;7(1):7-21 The Efficacy and Safety of Daclizumab and its Potential Role in the Treatment of Multiple Sclerosis

Ron Milo, MD Department of Neurology, Barzilai Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, 2 Hahistadrut St, Ashkelon 78278, Israel rmilo@gov.il

The Potential Role of Daclizumab in the Treatment of MS

Daclizumab constitutes a new avenue in the research and treatment of MS. The original assumption that blocking IL-2 signaling in T cells with daclizumab will lead to inhibition of effector T cells has been replaced by the elucidation of serendipitous and unexpected effects on both the innate and adaptive immune systems in MS, involving expansion of CD56bright NK cells, inhibition of T-cell activation by dendritic cells and inhibition of LTi cells. These discoveries have been made through a series of in vivo observations and mechanistic in vitro studies conducted along with initial clinical trials in active MS patients that demonstrated robust effect of daclizumab on inflammatory disease activity and suggested the expansion of CD56bright NK cells as a biomarker for daclizumab activity. Large phase IIb clinical trials added support to the beneficial effect of daclizumab treatment on clinical and MRI outcomes both as add-on and as monotherapy in RRMS that is sustained and may even increase over 2 years. The emergence of new and potentially serious AEs associated with daclizumab treatment may require strict monitoring programs. In any case, more definite results from ongoing phase III clinical trials are needed in order to verify the actual efficacy and safety of daclizumab in MS, and are eagerly awaited.