The increasing importance of the integral roles that IL-23 and IL-17 play in development of psoriatic plaques have led to clinical development of a number of humanized monoclonal antibodies (mAbs) that target these cytokines. Antagonists to IL-23, a heterodimeric cytokine comprising the IL-12p40 and p19 subunits, are believed to reduce plaque psoriasis by decreasing IL-23. Agents that bind to and inhibit IL-17A, one of 6 IL-17 homodimers, block inflammatory changes that lead to psoriasis.5

The primary objectives of clinical trials of biologics for the treatment of moderate-to-severe plaque psoriasis focus on outcomes that include a Physician’s Global Assessment (PGA) score of clear or minimal (0 or 1) and a Psoriasis Area and Severity Index (PSAI) reduction of at least 75% (PASI 75). In addition, the validated, self-reported Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO) instrument can be used to quantify the effect of psoriasis on work-related activities.2

Ixekizumab Targets IL-17A


Continue Reading

The newest agent, approved by the FDA on March 22, 2016 is ixekizumab, a humanized 17A IgG4 mAb with a high binding affinity to IL-17A.5 Three phase 3 studies, UNCOVER 1, UNCOVER-2, and UNCOVER-3, showed that among more than 3,800 patients treated with ixekizumab 160 mg starting dose, followed by 80mg every 2 or 4 weeks, PASI 75 scores were achieved in 89%, 90%, and 87% of patients, respectively, at 12 weeks, with the agents showing continued efficacy through week 60. In UNCOVER-1, these scores were significantly higher than placebo, 3.9% (P<0.001)5 and, in UNCOVER-2 and UNCOVER-3, significantly higher than the 41.6% to 53.4% observed with the active comparator, etanercept 50mg twice weekly. In UNCOVER-2 and UNCOVER-3, 30.8% to 40.5% of the patients treated with ixekizumab achieved PASI 100 at 12 weeks, with high levels of responses reported through 60 weeks.4 The most frequently reported adverse events were injection site reactions, nasopharyngitis, and headache.5

When the effect of ixekizumab treatment on work productivity was measured using the WPAI-PSO as completed by patients in all of the UNCOVER trials, both short- and long-term improvements were reported compared with placebo. Among patients treated with ixekizumab who had achieved a clinical response at 12 weeks, improvements in WPAI-PSO scores were sustained through 60 weeks. Therefore, treatment with ixekizumab has the potential to lead to a reduced cost burden, not only for patients but their families and society.2