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Psoriasis
Challenges in Managing Psoriasis – Opinion on Biologic Therapies
Jörg Christoph Prinz
Professor, Department of Dermatology, University of Munich
Abstract
Psoriasis vulgaris is a chronic inflammatory skin disorder associated with several co-morbidities and a greatly reduced quality of life. As psoriasis
is a lifelong condition, conventional systemic therapies are of limited value as they have cumulative toxic effects. Recent advances in the
understanding of the immunopathogenesis of psoriasis have led to the development of biological agents designed to target the molecular
mechanisms of the condition. This article assesses the biological therapies infliximab, adalimumab, efalizumab, etanercept and ustekinumab in
terms of meeting the therapeutic challenges of psoriasis. Clinical trials have demonstrated induction of remission and improved quality of life
with all biological therapies, infliximab being the most effective in the short term. Infliximab, adalimumab, etanercept and ustekinumab have
been demonstrated to be efficacious in the treatment of psoriatic arthritis. However, the recent suspension of efalizumab due to safety concerns
has raised fears regarding other biological agents. There are considerable data to suggest etanercept treatment is associated with few adverse
events compared with infliximab, adalimumab and efalizumab (limited safety data are available to date regarding ustekinumab). Moreover, only
etanercept has a number of studies demonstrating long-term efficacy, and its efficacy is not lost on re-treatment. No rebound effects have been
noted following discontinuation of treatment. It is also the only biological therapy for which efficacy has been demonstrated in psoriasis in
children. The author concludes that, at present, etanercept is the most balanced option in meeting all the challenges of psoriasis therapy.
Keywords
Psoriasis vulgaris, psoriatic arthritis, infliximab, adalimumab, etanercept, efalizumab, ustekinumab, tumour necrosis factor-alpha (TNF-α)
antagonist, T-cell antagonist, safety, long-term efficacy, remission
Disclosure: Jörg Christoph Prinz has acted as a principal investigator, consultant or speaker for Biogen(-Idec), Essex Pharma, Galderma Laboratories, Novartis, Merck-Serono,
Janssen-Cilag, Wyeth Pharmaceuticals, Abbott Laboratories and Centocor Inc.
Received: 7 May 2009 Accepted: 20 May 2009
Joerg.Prinz@med.uni-muenchen.de
Psoriasis vulgaris is a chronic inflammatory skin disorder with various central role. Dendritic cells (DCs) promote the activation and
clinical manifestations, including guttate and chronic plaque maturation of T cells within the skin. DC- and T-cell-derived cytokines
psoriasis, which account for around 80% of cases, erythrodermic, then promote the inflammatory epidermal hyperplasia by producing a
palmo-plantar or inverse psoriasis and psoriasis pustulosa (pustular typical pattern of cytokines that is dominated by tumour necrosis
psoriasis). Up to 30% of patients develop psoriatic arthritis (PsA). factor (TNF)-α, interleukin (IL)-17, interferon (IFN)-γ and IL-22.
3,4
Psoriasis generally presents before 35 years of age – the highest
frequency of disease onset is in those 18–20 years of age – and is Introduction to Biologic Treatments
usually a lifelong relapsing disease resulting in a greatly reduced Conventional systemic treatments include methotrexate, acitretin
quality of life (QoL). Its average duration is much longer than that of and cyclosporine, but their long-term use is associated with
most other major medical disorders (see Figure 1). Furthermore, cumulative organ toxicity, which may limit their therapeutic use.
various co-morbidities are associated with psoriasis: autoimmune Biologic therapies provide selective intervention at key steps in the
conditions such as Crohn’s disease and ulcerative colitis affect pathogenesis of the disease by interacting with T-cell activation and
approximately 10–11 and 6% of patients, respectively, while other function or with cytokines. By neutralising essential cytokines of the
conditions occasionally seen with psoriasis include eye inflammation inflammatory cascade, anti-TNF-α and anti-IL-12/IL-23 agents have
such as iritis and iridocyclitis, nail disease and psychological effects been demonstrated to relieve symptoms of both psoriasis and PsA
such as reactive depression, suicidal tendencies and alcoholism. The and arrest disease progression.
metabolic syndrome and cardiovascular diseases may develop in
direct correlation with the duration and severity of psoriasis; these The European Medicines Agency (EMEA) and the US Food and Drug
disorders aggravate psoriasis morbidity and, by increasing Administration (FDA) have approved the following biological agents:
cardiovascular mortality, reduce life expectancy by 3.5–4.5 years.
1,2
efalizumab (suspended 2009), etanercept, infliximab, adalimumab,
5
ustekinumab and alefacept (US and Switzerland only). They can be
The exact aetiology of psoriasis is unclear, although it is now widely classified according to their mechanism of action: T-cell antagonists,
accepted that immune-mediated inflammatory alterations play a TNF-α antagonists and an IL-12/IL23 p40 agonist. The T-cell
2 © TOUCH BRIEFINGS 2009
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