New Therapies for Psoriasis and Psoriatic Arthritis

Christopher T. Ritchlin; James G. Krueger

Disclosures

Curr Opin Rheumatol. 2016;28(3):204-210. 

In This Article

Abstract and Introduction

Abstract

Purpose of review Over the last several years, novel immunologic pathways pivotal in the development of the pathobiology of psoriasis and psoriatic arthritis (PsA) have been revealed. These discoveries catalyzed a search for new treatment targets resulting in many new therapies that are now available for patients with psoriatic disease.

Recent findings Helper T cells that secrete interleukin-17 (TH17) along with CD8+ cells, innate lymphocyte cells, and gamma delta T cells are important in the pathogenesis of psoriasis and PsA. Recently, agents that target interleukin-17, the interleukin-17 receptor, and interleukin-23 (antip19) have been approved or are in clinical trials. Apremilast, a new oral agent, was approved for the treatment of psoriasis and PsA.

Summary Secukinumab, an interleukin-17A antibody, has been approved for treatment of psoriasis and PsA in the United States. It is effective with a good safety profile. Ixekizumab, another anti-interleukin-17A antibody, is currently in clinical trials and brodalumab, an interleukin-17 receptor antagonist, was removed from clinical trials because of safety concerns despite demonstrated efficacy in psoriasis and PsA. Targeting interleukin-23 with antibodies to p19 is another approach with encouraging results in psoriasis. Apremilast, an oral agent, approved to treat psoriasis and PsA demonstrates moderate efficacy with an excellent safety record. The role of tofacitinib in psoriatic disease remains to be determined pending a safety review in psoriasis and completion of PsA trials.

Introduction

Psoriasis vulgaris is an autoimmune disease of the skin, but it is associated with systemic inflammation and co-morbid conditions that are linked to inflammatory processes, e.g., metabolic syndrome, cardiovascular disease, inflammatory bowel disease, and inflammatory arthritis.[1] Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis characterized by heterogeneous musculoskeletal phenotypes that involve multiple domains including the peripheral joints, axial skeleton, insertion sites (entheses), and digits (dactylitis).[2] Therapeutic options for the treatment of both psoriasis and PsA have increased dramatically over the past 15 years resulting in markedly improved outcomes for skin and joint disease. Consider that at the turn of the century the main therapies for moderate to severe psoriasis were topical agents, phototherapy, methotrexate, and cyclosporine. Therapies for PsA included methotrexate, sulfasalazine, and injectable corticosteroids. The arrival of anti-Tumor Necrosis Factor (TNF) agents represented a major treatment advance because these therapies were very effective for psoriasis and all the musculoskeletal domains of PsA. Despite improved outcomes, approximately 45% of psoriasis and PsA patients did not achieve the Psoriasis and Severity Index (PASI) 75 skin response or American College of Rheumatology response criteria (ACR) 20 composite joint outcome, respectively.

Advances in our understanding of immunologic pathways revealed that molecules in the interleukin-23-interleukin-17 pathway are critical to host defense against staphylococcus, candida, and other pathogens and that these molecules also promote skin and joint inflammation.[3] On the account of these discoveries, efforts to target molecules in the interleukin-23-interleukin-17 and phosphodiesterase E4 (PDE4) pathway to treat psoriasis and inflammatory arthritis commenced resulting in an array of approved therapies for both psoriasis and PsA. In this review, we will discuss linkage between our revised conceptual understanding of the pathobiology of psoriasis and PsA and the recent therapies that target pathways crucial for the development of skin and joint inflammation. We will also discuss pivotal clinical trials highlighting the efficacy and safety of the new biologic therapies for psoriatic disease.

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