Daclizumab Case Study Solution

Daclizumab (Biogen Idec and Abbott Biotherapeutics Corp.) is a humanized mAb acting as a blocker of the α-subunit (CD25) of the high-affinity IL-2 receptor [19]. IL-2 is secreted by activated lymphocytes and stimulates production of other proinflammatory cytokines while it is also involved in lymphocytic proliferation. Daclizumab was initially approved for the prevention of renal allograft rejection as part of a combination regimen and evidence was progressively accumulated showing that this drug could also be effective in other diseases, such as non-infectious uveitis [30,31] and MS [32-38].
After demonstrating that the drug could be effective in animal models of the disease, 10 patients diagnosed with RRMS and secondary progressive MS (SPMS)
This was also a 1-year, double-blind, randomised and controlled study with 517 patients who participated in the SELECT trial. The results were recently published [38] and, basically, SELECT patients under treatment with daclizumab HYP 150 or 300 mg were either randomised to a washout period of 24 weeks and then reinitiated on their original dose or stayed on the same dose for 1 year more, in a 1:1 proportion. Those previously receiving placebo either received daclizumab HYP 150 or 300 mg again in a 1:1 proportion during 1 year. In these patients, the relapse rate at the end of the study was reduced by 59% (p<0.001), with no discrimination between the two different doses of the mAb. The number of new or enlarging T2 lesions was 8.0 after the first year on placebo and switching to daclizumab in the SELECTION trial justified a reduction of 74% in this parameter (p<0.0001). Also the number of gadolinium-enhancing lesions was reduced by 86% in patients receiving the mAb after 52 weeks on placebo (p<0.0001). In patients continuing on daclizumab, the relapse rate on the second year did not change compared with the first year under treatment and the reduction of new or enlarging T2 lesions was more evident in the second year for both the doses of the mAb. After a washout period of 24 weeks, it was not possible to identify any MRI rebound effect. The safety and tolerability issues were similar to those previously identified in the SELECT trial [38]. However, one patient receiving daclizumab 300 mg died from autoimmune hepatitis and in the previous SELECT study another patient died from a psoas abscess (in recovering from a cutaneous adverse event). These