Daclizumab is a humanized monoclonal antibody that binds to the α subunit (CD25) of the interleukin-2 receptor and favorably modulates the immune environment in multiple sclerosis (MS). Blockage of CD25, among other effects, causes expansion and enhanced function of regulatory CD56bright natural killer cells, which seems to be the leading mechanism of action in MS. Phase II and III clinical trials have demonstrated that monthly subcutaneous injections of daclizumab high yield process (DAC HYP) 150 mg in patients with relapsing MS led to a significant reduction of annualized relapse rate and decreased number of contrast-enhanced lesions on brain magnetic resonance imaging. Treatment with DAC HYP had efficacy superior to treatment with weekly injections of interferon β1a. This review summarizes the development of and clinical experience with daclizumab in MS.

Department of Neurology and Center of Clinical Neuroscience Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Praha 2 Praha 121 08 Czech Republic

Department of Neurology and Center of Clinical Neuroscience Charles University Prague Faculty of Medicine and General University Hospital Prague Praha Czech Republic

See more in PubMed

Bielekova B. (2013) Daclizumab therapy for multiple sclerosis. Neurotherapeutics 10: 55–67. PubMed PMC

Bielekova B., Catalfamo M., Reichert-Scrivner S., Packer A., Cerna M., Waldmann T., et al. (2006) Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A 103: 5941–5946. PubMed PMC

Bielekova B., Howard T., Packer A., Richert N., Blevins G., Ohayon J., et al. (2009) Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol 66: 483–489. PubMed PMC

Bielekova B., Richert N., Herman M., Ohayon J., Waldmann T., McFarland H., et al. (2011) Intrathecal effects of daclizumab treatment of multiple sclerosis. Neurology 77: 1877–1886. PubMed PMC

Bielekova B., Richert N., Howard T., Blevins G., Markovic-Plese S., McCartin J., et al. (2004) Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proc Natl Acad Sci U S A 101: 8705–8708. PubMed PMC

Boyman O., Sprent J. (2012) The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 12: 180–190. PubMed

Cheng G., Yu A., Malek T. (2011) T-cell tolerance and the multi-functional role of IL-2R signaling in T-regulatory cells. Immunol Rev 241: 63–76. PubMed PMC

Cortese I., Ohayon J., Fenton K., Lee C., Raffeld M., Cowen E., et al. (2016) Cutaneous adverse events in multiple sclerosis patients treated with daclizumab. Neurology 86: 847–855. PubMed PMC

Diao L., Hang Y., Othman A., Nestorov I., Tran J. (2016) Population pharmacokinetics of daclizumab high-yield process in healthy volunteers and subjects with multiple sclerosis: analysis of phase I-III clinical trials. Clin Pharmacokinet 55: 943–955. PubMed

Giovannoni G., Gold R., Selmaj K., Havrdova E., Montalban X., Radue E., et al. (2014) Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial. Lancet Neurol 13: 472–481. PubMed

Gold R., Giovannoni G., Selmaj K., Havrdova E., Montalban X., Radue E., et al. (2013) Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet 381: 2167–2175. PubMed

Gold R., Radue E., Giovannoni G., Selmaj K., Havrdova E., Stefoski D., et al. (2016) Safety and efficacy of daclizumab in relapsing-remitting multiple sclerosis: 3-year results from the SELECTED open-label extension study. BMC Neurol 16: 117. PubMed PMC

Kappos L., Wiendl H., Selmaj K., Arnold D., Havrdova E., Boyko A., et al. (2015) Daclizumab HYP versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med 373: 1418–1428. PubMed

Krueger J., Kircik L., Hougeir F., Friedman A., You X., Lucas N., et al. (2016) Cutaneous adverse events in the randomized, double-blind, active-comparator decide study of daclizumab high-yield process versus intramuscular interferon beta-1a in relapsing-remitting multiple sclerosis. Adv Ther 33: 1231–1245. PubMed PMC

Liao W., Lin J., Leonard W. (2013) Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity 38: 13–25. PubMed PMC

Lowe C., Cooper J., Brusko T., Walker N., Smyth D., Bailey R., et al. (2007) Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet 39: 1074–1082. PubMed

Markovic-Plese S., Pinilla C., Martin R. (2004) The initiation of the autoimmune response in multiple sclerosis. Clin Neurol Neurosurg 106: 218–222. PubMed

Martin J., Perry J., Jakhete N., Wang X., Bielekova B. (2010) An IL-2 paradox: blocking CD25 on T cells induces IL-2-driven activation of CD56(bright) NK cells. J Immunol 185: 1311–1320. PubMed PMC

Oh J., Saidha S., Cortese I., Ohayon J., Bielekova B., Calabresi P., et al. (2014) Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis. Neurology 82: 984–988. PubMed PMC

Oh U., Blevins G., Griffith C., Richert N., Maric D., Lee C., et al. (2009) Regulatory T cells are reduced during anti-CD25 antibody treatment of multiple sclerosis. Arch Neurol 66: 471–479. PubMed PMC

Ohayon J., Oh U., Richert N., Martin J., Vortmeyer A., McFarland H., et al. (2013) CNS vasculitis in a patient with MS on daclizumab monotherapy. Neurology 80: 453–457. PubMed PMC

PharmaTimes (2006) PharmaTimes online 23 November 2006. Available at: http://www.Pharmatimes.Com/news/roche_ducks_out_of_transplant_drug_alliance_995643 (accessed 21 September 2016).

Radue E., Sprenger T., Vollmer T., Giovannoni G., Gold R., Havrdova E., et al. (2016) Daclizumab high-yield process reduced the evolution of new gadolinium-enhancing lesions to T1 black holes in patients with relapsing-remitting multiple sclerosis. Eur J Neurol 23: 412–415. PubMed

Radue E., Stefoski D., Gold R., McNeill M., Riester K., Elkins J. (2014) Reduction in brain atrophy with extended daclizumab HYP treatment: results of SELECT and the SELECT extension study. Neurology 82(Suppl. 10): P3.187.

Rose J., Burns J., Bjorklund J., Klein J., Watt H., Carlson N. (2007) Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results. Neurology 69: 785–789. PubMed

Rose J., Watt H., White A., Carlson N. (2004) Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol 56: 864–867. PubMed

Smith K. (2006) The structure of IL2 bound to the three chains of the IL2 receptor and how signaling occurs. Med Immunol 5: 3. PubMed PMC

Stankiewicz J., Kolb H., Karni A., Weiner H. (2013) Role of immunosuppressive therapy for the treatment of multiple sclerosis. Neurotherapeutics 10: 77–88. PubMed PMC

Tran J., Othman A., Mikulskis A., Wolstencroft P., Elkins J. (2016) Pharmacokinetics of daclizumab high-yield process with repeated administration of the clinical subcutaneous regimen in patients with relapsing-remitting multiple sclerosis. Clin Pharmacol 8: 9–13. PubMed PMC

Waldmann T. (1993) The IL-2/IL-2 receptor system: a target for rational immune intervention. Immunol Today 14: 264–270. PubMed

Waldmann T. (2007) Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol 27: 1–18. PubMed

Wiendl H., Gross C. (2013) Modulation of IL-2Ralpha with daclizumab for treatment of multiple sclerosis. Nat Rev Neurol 9: 394–404. PubMed

Wiseman L., Faulds D. (1999) Daclizumab: a review of its use in the prevention of acute rejection in renal transplant recipients. Drugs 58: 1029–1042. PubMed

Wuest S., Edwan J., Martin J., Han S., Perry J., Cartagena C., et al. (2011) A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy. Nat Med 17: 604–609. PubMed PMC

Wynn D., Kaufman M., Montalban X., Vollmer T., Simon J., Elkins J., et al. (2010) Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase II, randomised, double-blind, placebo-controlled, add-on trial with interferon beta. Lancet Neurol 9: 381–390. PubMed

Zinbryta (2016) Package insert. Biogen and AbbVie Inc., 1 June 2016.