Results from three phase 3 trials, suggest ixekizumab (Talz, Eli Lilly & Company) is effective through 60 weeks of treatment among patients with moderate-to-severe plaque psoriasis, according to a new article published in the New England Journal of Medicine. The humanized IgG4 monoclonal antibody, selectively binds with interleukin 17A (IL-17A) cytokine, inhibiting its interaction with the IL-17 receptor.
Researchers reported on the Eli Lilly-funded UNCOVER-1, UNCOVER-2 and UNCOVER-3 studies, which evaluated the safety and efficacy of 80 mg of ixekizumab, every two weeks, following a 160-mg starting dose, compared to placebo after 12 weeks. The studies also looked at response rates with ixekizumab every four weeks through 60 weeks. UNCOVER-2 and UNCOVER-3 included an additional arm for comparison, in which patients received etanercept 50 mg, twice weekly for 12 weeks.
Primary endpoints at 12 weeks were Psoriasis Area Severity Index (PASI) score 75 and static Physicianâs Global Assessment score [sPGA] 0, which is clear, or 1, minimal psoriasis. In all three studies, researchers also assessed sPGA and PASI through 60 weeks.
In UNCOVER-1, 81.8 percent of patients treated with ixekizumab achieved sPGA 0 or 1, versus 3.2 percent in the placebo arm. Nearly 90 percent of patients treated with ixekizumab achieved PASI 75 compared to 3.9 percent in the placebo group. Among those in the active arm, 70.9 percent achieved PASI 90 versus 0.5 percent of those treated with placebo. And 35.3 percent of subjects treated with ixekizumab achieved PASI 100 compared to zero patients treated with placebo.
In UNCOVER-1 and UNCOVER-2 through 60 weeks, 78.3 percent of subjects maintained an sPGA 0 or 1; 83.3 percent of patients achieved PASI 75; 76.5 percent achieved PASI 90; and 57.5 percent achieved PASI 100.
In UNCOVER-3, in which ixekizumab was given every four weeks through 60 weeks among patients initially treated with the drug every two weeks, 74.5 percent achieved sPGA 0 or 1; 83.4 percent achieved PASI 75; 73.2 percent achieved PASI 90; and 55.3 percent achieved PASI 100.
The authors conclude the benefits of ixekizumab need to be weighed against adverse event risks, which include upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections, as well as serious hypersensitivity reactions and inflammatory bowel disease.