The Latest Drugs and Small Molecule Inhibitors for Skin and Hair

December 2017 | Volume 16 | Issue 12 | Original Article | 1224 | Copyright © 2017

Varun Kalhana and Neil Sadick MDb

aTouro College of Osteopathic Medicine, Middletown, NY bWeill Cornell Medical College, Cornell University, New York, N

Abstract

Biologic drugs, a novel class of agents engineered to target specifc mediators of infammation, and small-molecule inhibitors that pen-etrate the cell membrane to interact with targets inside a cell represent the cutting-edge of pharmacological biomedical therapeutics. Clinical studies have already demonstrated the effectiveness of this new generation of drugs in treating a variety of medical illnesses and conditions that were refractory to traditional treatments. This review aims to describe the latest available or currently in-develop-ment drugs, biologic agents, and small molecule inhibitors for treatment of psoriasis, rosacea, alopecia areata, and atopic dermatitis.

J Drugs Dermatol. 2017;16(12):1224-1228

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INTRODUCTION

Biologic drugs are a novel class of pharmacological agents, isolated from a variety of natural sources, engineered to target specific mediators of inflammation. They represent the cutting-edge of biomedical research and, in time, may offer the most effective means to treat a variety of conditions that presently have limited to no treatments available.1 The latest biologics that have been introduced and used in various medical elds are those that target tumor necrosis factor TNFa, interleukin IL12/23, and IL-17. Their integration in patient treatment regimens has proven to improve treatment, with greater efficacy and better overall safety profile than early biologics and traditional systemic agents. While effective however biologics have their set of limitations: many are delivered via injection, which may deter patient, 2 drug adherence can be limited over time and the cost can be prohibitive compared to traditional systemic therapy.2-4 Development of small-molecule drugs that block errant cell signaling pathways is another active field with the goal to provide breakthroughs in topical treatments. Small molecules can penetrate the cell membrane to interact with targets inside a cell, typically interfering with the enzymatic activity of a target protein.5,6 Although small molecules tend to be less effective and just as expensive than biologics, they offer advantages such as not requiring regular laboratory monitoring resulting in better patient compliance, ef cient skin penetration and an improved safety pro le compared to traditional treatments.3,4 Both small molecules and biologics have been used and are being developed for several dermatologic conditions such as psoriasis, rosacea, alopecia areata, and atopic dermatitis.7-9 This review aims to describe the developments in this field that are available or currently in-development based on their proven efficacy in treating different clinical manifestations associated with dermatologic conditions based on available published data.

Psoriasis

Psoriasis affects approximately 1–3% of the worldwide adult population and approximately 3–4% of adults in the United States.10,11 Conventional treatment approaches for moderate-to-severe psoriasis include phototherapy and systemic therapies such as methotrexate, cyclosporine, and acitretin. Although these therapies provide disease control, they lose effectiveness over time due to side-effects that arise with long-term exposure and patient discontinuation.12-14 Several small molecules and biologics with promising results have been FDA-approved recently to target psoriasis (Table 1). Apremilast (Otezla®), an oral phosphodiesterase-4 (PDE4) inhibitor, received FDA approval in 2014 for the treatment of psoriatic arthritis and plaque psoriasis. Apremilast decreases pro-inflammatory mediators (TNF-α, IL-17, IL-23) and increases anti-inflammatory mediators.15-17 Phase III data showed a significant response in plaque psoriasis at weeks 16 and 52: 61% of patients experienced 75% improvement with no serious side effects.17 Apremilast also significantly reduced pruritus and skin discomfort/pain severity.15 Tofacitinib (Xeljanz®) a Janus kinase inhibitor (JAK) that blocks signaling of key cytokines associated with immune response and inflammation is FDA approved for rheumatoid arthritis and has shown promising results for moderate to severe chronic plaque psoriasis12,18 Phase III data showed improvements in Psoriasis Area & Severity Index (PASI) 75 response at week 16 with no severe side effects.12,18

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