Ixekizumab for the Treatment of Psoriasis: A Review of Phase III Trials

Abstract

IntroductionInterleukin-17 inhibitors are the newest class of monoclonal antibodies approved by the US Food and Drug Administration for the treatment of psoriasis. Preclinical and Phase II studies of ixekizumab, a high-affinity anti-IL-17A monoclonal antibody, have proved promising.MethodsWe conducted an extensive literature search using the PubMed database to assess the efficacy and safety profile of ixekizumab. The search included the following key words: “psoriasis” and “IL-17” or “ixekizumab.” We also reviewed citations within articles to identify relevant sources.ResultsBy week 12, the percentage of patients achieving a 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) was comparable among the three Phase III trials (UNCOVER-1, 89%; UNCOVER-2, 90%; UNCOVER-3, 87%). Ixekizumab continued to be efficacious through 60 weeks of treatment. The safety profile of ixekizumab was favorable; the most frequently reported adverse events consisted of nasopharyngitis, upper respiratory tract infection, injection-site reaction, and headache.ConclusionOverall, ixekizumab demonstrated rapid clinical improvement and favorable short-term safety profile in Phase III trials. The results support ixekizumab as an effective therapeutic option for patients with moderate-to-severe plaque-type psoriasis.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-016-0102-0) contains supplementary material, which is available to authorized users.

Efficacy and safety of interleukin‐17 antagonists in patients with plaque psoriasis: a meta‐analysis from phase 3 randomized controlled trials

“…analysed two trials in one paper. One trial evaluated the effects of brodalumab, and four articles including three RCTs evaluated the effects of ixekizumab vs. placebo. The pooled analysis included 5951 patients with moderate‐to‐severe plaque psoriasis (4216 randomized to IL‐17 antagonists and 1735 to placebo).…”

Histone modifications associated with biological drug response in moderate‐to‐severe psoriasis

“…Besides, the inclusion of patients treated with several drugs with different mechanism of action (adalimumab, ixekizumab secukinumab or ustekinumab) could act as a confounding factor. Moreover, as these drugs are highly effective, the number of patients that do not respond is low, thus reducing the statistical power of several comparisons. Further studies including a higher number of subjects treated with each drug should be performed in order to confirm these results.…”

“…The first biological approaches to treat the disease are anti‐TNF drugs such as adalimumab, infliximab and etanercept . Furthermore, alternative biological drugs are used to treat this disease such as ustekinumab (a monoclonal antibody that binds to the p40 subunit shared by IL‐12 and IL‐23) or secukinumab and ixekizumab (monoclonal antibodies that target IL‐17) . As biological drugs are expensive and, although rarely, they can cause severe secondary adverse effects, it is necessary to discover non‐invasive biomarkers that could predict drug response and facilitate treatment individualization for psoriasis patients.…”

Spotlight on ixekizumab for the treatment of moderate-to-severe plaque psoriasis: design, development, and use in therapy

“…Severe adverse events were reported in <2% of treated patients considering all the published studies 38–49. There were no deaths, and overall, an equal safety profile was observed between biologic-naïve and biologic-experienced patients 40,50.…”