Daclizumab

Daclizumab (trade name Zinbryta, by Biogen) is a therapeutic humanized monoclonal antibody which was used for the treatment of adults with relapsing forms of multiple sclerosis (MS). Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor of T-cells. Daclizumab (trade name Zinbryta, by Biogen) is a therapeutic humanized monoclonal antibody which was used for the treatment of adults with relapsing forms of multiple sclerosis (MS). Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor of T-cells. In March 2018, it was voluntarily withdrawn from the market by Biogen and Abbvie after reports of encephalitis in Europe. Daclizumab was used to treat adults with relapsing forms of multiple sclerosis. It is administered subcutaneously. In clinical trials it showed 45% decrease in annualized relapse rate, a 41% reduction in the proportion of patients who relapsed, and a 54% reduction in the number of new lesions. Daclizumab was approved and used to prevent acute rejection of kidney transplant, along with cyclosporine and corticosteroids. For that indication, side effects with a frequency of at least 10% included sleeplessness, tremor, headache, arterial hypertension, dyspnoea, gastrointestinal side effects and oedema. In rare cases, the drug could cause severe anaphylaxis. In the US, daclizumab is contraindicated in people with liver impairment, including significantly elevated liver enzymes (ALT, AST) and autoimmune hepatitis. The European Medicines Agency (EMA) originally approved the drug without any contraindications apart from known hypersensitivity, but required Biogen to implement a hepatic risk management guide for physicians. In July 2017, the EMA has issued a provisional contraindication for patients with pre-existing liver disease or liver impairment. In clinical trials for MS, there were no treatment-related deaths or increased risk of cancer; side effects that occurred more frequently with daclizumab versus interferon included infections (65% versus 57%), skin rashes (37% versus 19%) and liver complications (approximately 18% versus 12%). As an antibody, daclizumab is expected to have a very low potential for pharmacokinetic interactions with other drugs. Daclizumab blocks IL-2 receptors containing the alpha subunit (CD25), which include the high-affinity receptors. Medium-affinity receptors, on the other hand, consist of two beta subunits (CD122) and are not affected by daclizumab. While the exact mechanism is unknown, the net effect is a reduction of T-cell responses and expansion of CD56bright natural killer cells.