Psoriasis: a groundbreaking new treatment?

Katherine Kar Yee Law, University College London Medical School, University College London, Gower Street, London, WC1E 6BT

Psoriasis is a common, disfiguring, immune-mediated inflammatory skin disease affecting 2% of the population in the United Kingdom. It not only manifests as characteristic scaling skin rashes and plaques on the skin, but is also associated with pruritus, pain, arthropathy and a three-fold increase in mortality from cardiovascular disease. Due to the chronic, incurable nature of the disease and its severe impact on the quality of life, anxiety and depression also affects up to 25% of patients with psoriasis (1).

Current treatment strategies aim to control disease activity. For milder disease, topical agents such as vitamin D analogues and corticosteroids are used. Phototherapy using ultraviolet B light has also been shown to be beneficial. Immunosuppressive agents, such as methotrexate and ciclosporin, can bring short-term benefits but their adverse effects have precluded their long term use for severe psoriasis (2).

With a better understanding of the immunological basis of psoriasis, there has been development of newer agents (often termed ‘biologics’) which blocks molecular steps in the pathogenesis of psoriasis to improve efficacy of treatment and also minimise systemic toxicity. Currently biologic treatment can be divided into two groups – agents that target the cytokine tumour necrosis factor α (etanercept and infliximab) and agents that target T cells or antigen presenting cells (for example, efalizumab).

In a recent study published in the New English Journal of Medicine, the efficacy of a new type of biologic agent, brodalumab (an anti-Interleukin-17 receptor antibody) was studied. Interleukin-17 is a cytokine that is involved in the potent mediator in delayed-type reactions and autoimmune conditions. It has been shown significantly improve symptoms and quality of life in patients with moderate to severe plaque psoriasis (3).

In this phase 2 randomised, double-blind, placebo-controlled, dose-ranging study, 198 patients with a score of 12 or higher on the psoriasis area-and-severity index (PASI) and with 10% or more of their body-surface area affected receive either brodalumab at different doses or placebo for 12 weeks. Results show that the mean percentage improvements in the PASI score were 45.0% among patients receiving 70 mg of brodalumab, 85.9% among those receiving 140 mg, 86.3% among those receiving 210 mg, 76.0% among those receiving 280 mg, and 16.0% among those receiving placebo.

The finding suggests that brodalumab can dramatically improve the presentation of psoriasis in patients with moderate to severe disease. Although the study is limited by the small sample population and is potentially biased as it was conducted by the pharmaceutical company producing the treatment, it demonstrates that this biologic may be useful in the treatment of psoriasis. This opens up promising treatment options for patients constantly living with this debilitating and disfiguring disease.

References: 

1. Smith CH, Baker JN. Psoriasis and its management. BMJ 2006 Aug 19; 333(7564):380-4. doi:10.1136/bmj.333.7564.380

2. Winterfield LS, Menter A, Gordon K, Gottlieb A. Psoriasis treatment: current and emerging directed therapies. Ann Rheum Dis 2005 Mar; 64 Suppl 2:ii87-ii90; discussion ii91-2. doi:10.1136/ard.2004.032276

3. Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, Aras G, Li J, Russell CE, Thompson EHZ, Baumgartner S. Brodalumab, an anti–interleukin-17–receptor antibody for psoriasis. N Engl J Med 2012 Mar29; 366(13):1181-9. doi:10.1056/NEJMoa1109997

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