Revisiting Daclizumab for Multiple Sclerosis: A Systematic Evaluation of a Targeted Immunotherapy

BACKGROUND: Daclizumab is a humanized monoclonal antibody that blocks the interleukin-2 receptor α-chain (CD25) and reduces activation of auto reactive T cells. It attenuates disease activity by reducing gadolinium-enhancing lesions in patients with relapsing-remitting multiple sclerosis (MS). Therefore, this systematic review aimed to revisit the therapeutic role of Daclizumab in MS patients with a particular focus on immune system parameters and its adverse events. MATERIALS AND METHODS: This systematic literature review included all published clinical trials from 2000 to 2025 regardless of publication date or language, identified through searches of Embase, Medline, Cochrane, Scopus, and other databases. RESULTS: Daclizumab reduced the relapse frequency and disease activity; however, it was associated with serious safety concerns. The common complication in most patients with multiple sclerosis was hepatotoxicity and elevated liver enzymes. Furthermore, the cutaneous side effects occurred in 19-34% of patients, from mild rashes to serious dermatologic disorders such as psoriasis. Also, it was associated with an increased rate of upper respiratory infections in multiple sclerosis patients. Daclizumab therapy also promoted the expansion of CD56^bright^ natural killer (NK) cells and reduced the number of CD4+ T cells and CD25+ Foxp3- T regulatory cells. CONCLUSION: These findings suggest that Daclizumab may demonstrate promising treatment effects in MS patients by affecting the IL-2 receptor signaling pathway, modulating lymphocyte activity, and improving MS symptoms. However, because of documented complications, more research strategies are needed, and current treatment protocols should be revised.