Eli Lilly and Company announced Monday that JAMA Dermatology has published detailed results from three pivotal Phase 3 trials that evaluated the effect of ixekizumab on work productivity in patients with moderate-to-severe plaque psoriasis. Specific results from the UNCOVER-1 study were also presented Monday during the American Academy of Dermatology (AAD) Annual Meeting in Washington, D.C.
In an analysis of the UNCOVER-1, UNCOVER-2 and UNCOVER-3 studies, the effect of ixekizumab on work productivity was evaluated by the change from baseline as measured by Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO) scores at 12 weeks. The validated, self-reported WPAI questionnaire is used to measure impairment of work activities due to general health or a specific condition.
In all three studies, patients treated with ixekizumab reported improved work productivity compared to patients treated with placebo. In UNCOVER-1, improvements in work productivity were also sustained up to 60 weeks in those who demonstrated initial clinical response to ixekizumab at 12 weeks.
“Psoriasis is a serious, systemic disease that can have a significant impact on a patient’s overall health and quality of life, including work productivity and overall activity levels,” said April Armstrong, M.D., MPH, corresponding study author and associate dean of clinical research at Keck School of Medicine of University of Southern California. “The results presented at AAD and detailed in JAMA Dermatology further reinforce published data supporting ixekizumab as a potential treatment for moderate-to-severe plaque psoriasis. If approved, ixekizumab may provide dermatologists with a new option to address both skin symptoms and health-related outcomes for patients, including work-related activities.”
In all three studies, patients treated with ixekizumab every two weeks demonstrated the following results at 12 weeks:
- In UNCOVER-1, patients treated with ixekizumab showed significantly greater improvement compared to placebo in all WPAI-PSO scores: absenteeism, presenteeism, work productivity loss and activity impairment (p < 0.001 for all comparison scores).
- In UNCOVER-2, patients treated with ixekizumab showed significantly greater improvement compared to placebo in all WPAI-PSO scores: absenteeism (p=0.016), presenteeism (p < 0.001), work productivity loss (p < 0.001) and activity impairment (p < 0.001). Patients treated with ixekizumab also showed significantly greater improvement in the following WPAI scores compared to those treated with etanercept: presenteeism, work productivity loss and activity impairment (p < 0.001 for all comparison scores).
- In UNCOVER-3, patients treated with ixekizumab showed statistically significant improvements compared to placebo in all WPAI-PSO scores: absenteeism (p=0.012), presenteeism (p < 0.001), work productivity loss (p < 0.001) and activity impairment (p < 0.001). Patients treated with ixekizumab also showed significantly greater improvement in activity impairment scores compared to those treated with etanercept (p=0.009).
Improvements in WPAI scores were also sustained through 60 weeks among patients who achieved clinical response with ixekizumab at 12 weeks. In UNCOVER-1 and UNCOVER-2, significant improvements from baseline were sustained through 60 weeks among patients treated with ixekizumab for presenteeism, work productivity loss and activity impairment scores.
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.
In these studies, patients were randomized to receive different dosing regimens of ixekizumab (80 mg every two weeks or four weeks, following a 160-mg starting dose), or placebo, for 12 weeks. UNCOVER-2 and UNCOVER-3 included an additional comparator arm in which patients received etanercept (50 mg twice a week) for 12 weeks.
In addition, patients with moderate-to-severe plaque psoriasis who did not respond to treatment with etanercept achieved significant improvement in their psoriasis plaques when treated with ixekizumab in a Phase 3 clinical trial.
In UNCOVER-2, 64 percent (229/358) of patients treated with bi-weekly etanercept did not respond (static Physician’s Global Assessment score [sPGA] ≥2) to treatment at 12 weeks. These nonresponders were treated with placebo at 12 weeks, then received ixekizumab every four weeks from Weeks 16 through 60.
This study’s co-primary efficacy endpoints at 12 weeks of ixekizumab therapy were PASI 75 and sPGA 0 or 1. 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, while the sPGA is the physician’s assessment of severity of a patient’s psoriasis lesions overall at a specific point in time and is a required measure the FDA uses to evaluate effectiveness.1
Among those patients who did not respond to etanercept, the following was observed at 24 weeks of the study, 12 weeks following treatment with ixekizumab:
- 83.5 percent of patients achieved PASI 75;
- 57.0 percent of patients achieved PASI 90;
- 22.0 percent of patients achieved complete resolution of psoriasis plaques (PASI 100).
At 48 weeks following treatment with ixekizumab, the following was also observed at week 60 of the study among those who did not respond to etanercept:
- 82.5 percent of patients achieved PASI 75
- 68.5 percent of patients achieved PASI 90;
- 43.5 percent of patients achieved complete resolution of psoriasis plaques (PASI 100).
Additionally, 73 percent of those patients who did not respond to etanercept achieved sPGA 0 or 1 12 weeks after starting treatment with ixekizumab.
The majority of treatment-emergent adverse events were mild or moderate. The safety profile after receiving ixekizumab treatment was comparable among patients who initially received etanercept and patients who initially received placebo in this clinical trial.
“Despite the availability of existing treatment options, there are many patients living with moderate-to-severe plaque psoriasis who have not responded to previous treatments and are still looking for an alternative,” said Kim Papp, M.D., lead author and president, Probity Medical Research, Inc., Ontario, Canada. “In this study, ixekizumab demonstrated high levels of clearance for all patients. We saw high levels of improvement in biologic-experienced patients, and we saw high levels of improvement in those who have not been treated with a biologic. These results provide further evidence of a robust clinical data profile that, if approved, supports the use of ixekizumab in patients with moderate-to-severe plaque psoriasis.”
In UNCOVER-2, patients who did not respond to etanercept after 12 weeks of treatment demonstrated high levels of improvement in their moderate-to-severe plaque psoriasis after receiving treatment with ixekizumab.
Ixekizumab is the company’s investigational medicine for the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis.
Ixekizumab is an IgG4 monoclonal antibody that selectively binds with 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 pro-inflammatory cytokines and chemokines.
Psoriasis is a chronic, immune disease that affects the skin. It occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis affects approximately 7.5 million Americans and 125 million people worldwide, approximately 20 percent of whom have moderate-to-severe plaque psoriasis. Psoriasis can occur on any part of the body and is associated with other serious health conditions, such as diabetes and heart disease. The most common form of psoriasis, plaque psoriasis, appears as raised, red patches covered with a silvery white buildup of dead skin cells.