Ron Milo, Olaf Stüve

Multiple sclerosis (MS) is a chronic inflammatory-demyelinating disease of the central nervous system of a putative autoimmune etiology. Although the exact pathogenic mechanisms underlying demyelination and axonal damage in MS are not fully understood, T-cells are believed to play a central role in the pathogenesis of the disease. Daclizumab is a humanized binding monoclonal antibody that binds to the Tac epitope on the α-subunit (CD25) of the interleukin-2 (IL-2) receptor, thus effectively blocking the formation of the high-affinity IL-2 receptor, which is expressed mainly on T-cells. A series of clinical trials in patients with relapsing MS demonstrated a profound effect of daclizumab on inflammatory disease activity and improved clinical outcomes compared with placebo or interferon-β, which led to the recent approval of daclizumab (Zinbryta™) for the treatment of relapsing forms of MS. Enhancement of endogenous mechanisms of immune regulation rather than inhibition of effector T-cells might explain the effects of daclizumab in MS. These include expansion and improved function of regulatory CD56bright NK cells, inhibition of the early activation of T-cells through blockade of IL-2 transpresentation by dendritic cells and reduction in the number of intrathecal proinflammatory lymphoid tissue inducer cells. The enhanced efficacy of daclizumab is accompanied by an increased frequency of adverse events and risks of serious adverse events, thus placing it as a second-line therapy and calling for the implementation of a strict risk management program. This review details the mechanisms of action of daclizumab, discusses its efficacy and safety in patients with MS, and provides an insight into the place of this novel therapy in the treatment of MS.