Patients with moderate-to-severe plaque psoriasis who did not respond to treatment with etanercept (Enbrel, Amgen) achieved significant improvement in their psoriasis plaques when treated with ixekizumab (Eli Lilly) in a phase 3 study. Results from the UNCOVER-2 trial were presented at the American Academy of Dermatology annual meeting, taking place from March 4 to 8 in Washington, D.C.
Ixekizumab is an immunoglobulin 4 (IgG4) monoclonal antibody that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.
In the UNCOVER-2 trial, 64% (229/358) of patients treated with biweekly etanercept did not respond (static Physician’s Global Assessment [sPGA] score of 2 or greater) to treatment at 12 weeks. These nonresponders were treated with placebo at 12 weeks. They then received ixekizumab every four weeks from week 16 through week 60.
The study’s coprimary efficacy endpoints at week 12 were a 75% reduction in the Psoriasis Area Severity Index (PASI 75) and an sPGA score of 0 or 1. PASI measures the extent and severity of psoriasis by assessing the average redness, thickness, and scaliness of skin lesions (each graded on a scale of 0 to 4), weighted by the body surface area of involved skin, whereas the sPGA is the physician’s overall assessment of severity of a patient’s psoriasis lesions at a specific point in time. The sPGA is an effectiveness measure required by the FDA.
Among patients who did not respond to etanercept, the following results were observed at week 24 (after 12 weeks of monthly treatment with ixekizumab):
- 84% of patients achieved PASI 75.
- 57% of patients achieved PASI 90.
- 22% of patients achieved PASI 100 (complete resolution of psoriasis plaques).
At week 60 (after 48 weeks of monthly treatment with ixekizumab), the following results were observed among those who did not respond to etanercept:
- 83% of patients achieved PASI 75.
- 69% of patients achieved PASI 90.
- 44% of patients achieved PASI 100.
In addition, 73% of patients who did not respond to etanercept achieved an sPGA score of 0 or 1 at 12 weeks after starting treatment with ixekizumab.
Most treatment-emergent adverse events were mild or moderate in severity. The safety profiles of ixekizumab were comparable among patients who initially received etanercept and those who initially received placebo.
Source: Eli Lilly; March 7, 2016.