Ixekizumab demonstrates clinically meaningful improvements as early as one week among moderate-to-severe plaque psoriasis patients

Detailed results of this combined analysis of UNCOVER-2 and UNCOVER-3 were presented during the American Academy of Dermatology (AAD) Annual Meeting taking place March 4-8 in Washington, D.C.

UNCOVER-2 and UNCOVER-3 are double-blind, multicenter, Phase 3 studies evaluating more than 2,500 patients with moderate-to-severe plaque psoriasis across 19 countries.

In these comparator studies, patients were assigned to receive either placebo, etanercept (50 mg twice a week) or ixekizumab (80 mg every two or four weeks) for 12 weeks, following a 160-mg starting dose.

This combined analysis evaluated the speed of onset of clinical improvement as measured by mean percentage improvement in Psoriasis Area Severity Index (PASI) score from baseline, as well as time to PASI 50 and PASI 75 among patients treated with ixekizumab, etanercept or placebo. PASI measures the extent and severity of psoriasis by assessing average redness, thickness and scaliness of skin lesions (each graded on a zero to four scale), weighted by the body surface area of involved skin.

"Studies have shown that clinical improvement observed early during psoriasis treatment can help predict clinical response at later times," said Craig Leonardi, M.D., lead study author and clinical professor of dermatology at St. Louis University School of Medicine.

"In this analysis of ixekizumab, early results were seen in patients with moderate-to-severe plaque psoriasis, an extensive and difficult-to-treat disease. According to patients and their dermatologists, rapid clearing of psoriasis plaques is one of the most important attributes for treatment success."

Significant differences in mean percentage improvement of psoriasis plaques were observed among patients treated with ixekizumab compared to etanercept and placebo:

At one week, the mean percentage improvement was 32.7 percent in the group randomized to receive ixekizumab every two weeks, 10.3 percent in etanercept and 5.31 percent in placebo (p<0.001 for all comparisons).
At two weeks, the mean percentage improvement was 53.6 percent in the group randomized to receive ixekizumab every two weeks, 23.3 percent in etanercept and 9.25 etanercept in placebo (p<0.001 for all comparisons).

Treatment with ixekizumab also resulted in clinically meaningful improvements (PASI 50) as early as one week, which were statistically significantly different compared with etanercept and placebo.

At one week, PASI 50 was achieved by 22.8 percent of patients treated with ixekizumab every two weeks compared to 3.9 percent among those treated with etanercept and 1.4 percent in placebo (p<0.001 for all comparisons).
At two weeks, PASI 50 was achieved among 58.8 percent of patients treated with ixekizumab every two weeks compared to 14.6 percent of those treated with etanercept and 4.2 percent in placebo (p<0.001 for all comparisons).

Median time to PASI 75 was 30 days among patients treated with ixekizumab every two weeks and 85 days among those treated with etanercept.

The majority of treatment-emergent adverse events were mild or moderate. The most frequently reported adverse drug reactions were injection site reactions and upper respiratory tract infections (most frequently nasopharyngitis) and generally did not lead to treatment discontinuations. Overall, the safety profile was comparable to etanercept in these two clinical studies.

Ixekizumab is the company’s investigational medicine for the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis.