Fast track — ArticlesEtanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial
Introduction
In addition to its clinical symptoms, psoriasis is associated with substantial economic, emotional, and psychological effects.1, 2 In particular, depression has been documented as a significant disability in many patients;3 while severity of physical symptoms is responsible for some of the psychological effects, other factors, including environmental, cognitive, and life events also affect the psychological impact of skin disease.4 Studies have shown that health-related quality of life is impaired at baseline in patients with psoriasis and can be improved with treatment.5, 6, 7, 8, 9, 10 However, while most quality of life measures indirectly address aspectsof motivation and interest, depression has not been studied independently. In addition to the potentialbenefit for symptoms of depression related to psoriasis, increased concentrations of pro-inflammatory cytokines such as tumour necrosis factor α (TNFα) are associated with major depression, and it has beensuggested that reducing the effect of these cytokines may reverse depressive symptoms.11 Similarly, TNFα is associated with fatigue and sleepiness,12, 13, 14 andthere has been speculation that inflammatory cytokines might form a link between fatigue and depression.15
Etanercept is a soluble TNFα receptor that prevents TNFα-mediated cellular response by competitively inhibiting the interaction of TNFα with cell-surface receptors. Etanercept has been shown to be efficacious in patients with psoriasis in three separate studies.16, 17, 18 In this study, we further evaluated the effectiveness and adverse events associated with etanercept in patients with chronic, moderate-to-severe plaque psoriasis in a randomised, placebo-controlled, phase III clinical trial. In particular, we assessed the effect of etanercept on fatigue and symptoms of depression, both of which are common in the psoriasis population and are thought to be associated with increased levels of TNFα.
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Patients
All patients gave written informed consent before any study-related tests were done. Patients were eligible for study enrolment if they were aged 18 years or older with active, clinically stable plaque psoriasis involving 10% or more of total body surface area at screening. Patients were required to have a minimum psoriasis area and severity index (PASI) of 10 during screening and to have received at least one previous phototherapy or systemic therapy (or have been a candidate to do so in the
Results
39 investigative sites in the USA and Canada screened 749 patients for the study, and 620 patients were randomly assigned to a treatment group (figure 1). The first patient underwent randomisation in June, 2003; the final week-12 observation was made in January, 2004. 618 patients received at least one dose of investigational product and were included in the analyses (placebo n=307; etanercept n=311). Overall, 597 of the 618 patients completed the 12-week double-blind study period, 292 (95%) in
Discussion
In this Phase III study, we show that etanercept treatment results in meaningful improvement in fatigue and symptoms of depression in patients with psoriasis, and we reaffirm the treatment effect and adverse event profile previously reported for etanercept in patients with moderate to severe plaque psoriasis. Since the population enrolled in this trial was similar to those in previous studies of etanercept, and to those in studies examining other biological response mediators in plaque psoriasis
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