Rationale and Early Clinical Data on IL-17 Blockade in Psoriasis

Steven M Nwe; Amanda H Champlain; Kenneth B Gordon


Expert Rev Clin Immunol. 2013;9(7):677-682. 

In This Article


Ixekizumab, a humanized IgG4 monoclonal antibody administered by subcutaneous injection that targets the IL-17A cytokine has met with similar positive results. In its Phase II, double-blind, multicenter, randomized dose-ranging study, 142 subjects with moderate-to-severe plaque psoriasis were randomized to placebo or 10, 23, 75 or 150 mg of ixekizumab.[61] Subjects were dosed at 0, 2, 4, 8, 12 and 16 weeks. The primary end point was the percentage of patients who had a 75% or greater improvement in their PASI scores (PASI 75) at 12 weeks. At 12 weeks, 7.7, 76.7, 82.8 and 82.1% of the patients achieved PASI 75 in the 25, 75, 150 mg and placebo groups, respectively. Similar to brodalumab, the frequency of extremely high-level responses was very substantial.

Secondary end points included efficacy in quality life measures improvement. Significant improvements in subject quality of life, as seen by reductions in mean Dermatology Quality of Life Index scores, were seen as early as 8 weeks and were sustained through week 16. Also, in patients who reported an additional diagnosis of psoriatic arthritis, clinically significant improvements were seen in the 150 mg ixekizumab arm when compared with placebo at week 16 as measured by the joint-pain visual assessment scale. No serious adverse events occurred during the study, and the most common reported adverse events, similar to brodalumab, were nasopharyngitis, upper respiratory infection, injection site reactions and headaches. Asymptomatic, grade 2 neutropenia (i.e., 1000 to 1500 cells per cubic millimeter) occurred in two subjects on ixekizumab. Phase III studies for ixekizumab are currently underway.