A review of emerging IL-17 inhibitors in the treatment of psoriasis focusing on preclinical through phase II studies.

INTRODUCTION: Interleukin-17 has recently been identified as a key player in the pathogenesis of psoriasis. As such, several drugs targeting IL-17 are in various stages of clinical development. Areas covered: In this review, the authors describe several emerging therapies and drug candidates targeting IL-17. The authors detail many biologic injectable drug candidates as well as numerous potential oral and topical small molecule drug candidates. Expert opinion: Approval of IL-17 inhibitors has significantly improved the treatment options for psoriasis patients. Secukinumab and ixekizumab are approved in both Europe and the USA, and brodalumab is likely facing approval by the end of 2016. Numerous additional biologic and small molecule drug candidates are in the pipeline, and once deemed safe and effective will likely offer significant benefit to our psoriasis population.

Blue Nevus-Like Metastasis of a Cutaneous Melanoma Identified by Fluorescence In Situ Hybridization.

A blue nevus-like melanoma is a rare melanoma variant arising from or histologically similar to a blue nevus. It can be challenging to distinguish a cellular blue nevus from a blue nevus-like melanoma, particularly in cases of blue nevus-like melanoma lacking a transition from a clearly benign component. We present a case of a 78-year-old man who refused treatment for a previously existing melanoma and subsequently developed a gray nodule near the site of the previous melanoma. After fluorescence in situ hybridization revealed copy number gains in RREB1, this was diagnosed as a blue nevus-like metastatic melanoma. Blue nevus-like metastatic melanoma is most commonly seen near the site of the primary cutaneous melanoma. This entity should be considered in a patient with a history of melanoma and a new blue nevus-like lesion.

Radiation-induced localized bullous pemphigoid in a patient with breast carcinoma.

Bullous pemphigoid (BP) is a common pemphigoid disorder, which is localized in approximately 16-29% of cases. A small subset of localized BP cases is associated with prior radiation therapy, most commonly for breast carcinoma. We present a patient with an unusual presentation of localized BP after receiving partial accelerated breast irradiation (a type of brachytherapy that has a decreased amount of radiation to the skin as compared to the more common external beam radiation therapy).

A Review of Biologic Therapies Targeting IL-23 and IL-17 for Use in Moderate-to-Severe Plaque Psoriasis.

The development of several highly effective biologic drugs in the past decade has revolutionized the treatment of moderate-to-severe plaque psoriasis. With increased understanding of the immunopathogenesis of psoriasis, the emphasis has turned toward more specific targets for psoriasis drugs. Although the complex immunological pathway of psoriasis is not yet completely understood, current models emphasize the significant importance of interleukin (IL)-23 and IL-17. Several biologic drugs targeting these cytokines are now in various stages of drug development. Drugs targeting IL-23 include BI-655066, briakinumab, guselkumab, tildrakizumab, and ustekinumab. Drugs targeting IL-17 include brodalumab, ixekizumab, and secukinumab. While many of these have shown safety and good efficacy in clinical trials of moderate-to-severe plaque psoriasis, long-term safety is still to be established.

An overview of developing TNF-α targeted therapy for the treatment of psoriasis.

INTRODUCTION: Three biologic drugs targeting TNF-α are approved to treat moderate-to-severe cutaneous psoriasis. These are adalimumab, etanercept and infliximab. These drugs are given by subcutaneous injection or intravenous infusion, and while generally safe and effective, they are expensive with potential for side effects. Thus, numerous new drug candidates are under development that also target TNF-α. AREAS COVERED: In this review, the authors detail several drugs under development that target TNF-α, focusing on those drugs in preclinical, Phase I and II trials. The authors describe emerging biologic psoriasis therapies, including biosimilars and novel biologics, in addition to several synthetic and naturally derived small-molecule drug candidates. EXPERT OPINION: The currently approved TNF-α antagonists benefit from over 10 years of safety and efficacy data. The expense and method of administration of these biologics, however, can be cumbersome, and less expensive alternatives have the potential to benefit patients with psoriasis. It is inevitable, despite the introduction of new anti-IL-17 therapies, that established TNF-α targeted therapies, as well as newcomers targeting TNF-α, will continue to play an important role in the lifelong management of psoriasis.