Elsevier

The Lancet

Volume 367, Issue 9504, 7–13 January 2006, Pages 29-35
The Lancet

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Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial

https://doi.org/10.1016/S0140-6736(05)67763-XGet rights and content

Summary

Background

Psoriasis has substantial psychological and emotional effects. We assessed the effect of etanercept, an effective treatment for the clinical symptoms of psoriasis, on fatigue and symptoms of depression associated with the condition.

Methods

618 patients with moderate to severe psoriasis received double-blind treatment with placebo or 50 mg twice-weekly etanercept. The primary efficacy endpoint was a 75% or greater improvement from baseline in psoriasis area and severity index score (PASI 75) at week 12. Secondary and other endpoints included the functional assessment of chronic illness therapy fatigue (FACIT-F) scale, the Hamilton rating scale for depression (Ham-D), the Beck depression inventory (BDI), and adverse events. Efficacy analyses were based on the allocated treatment. Analyses and summaries of safety data were based on the actual treatment received. This study is registered with ClinicalTrials.gov with the identifier NCT00111449.

Findings

47% (147 of 311) of patients achieved PASI 75 at week 12, compared with 5% (15 of 306) of those receiving placebo (p<0·0001; difference 42%, 95% CI 36–48). Greater proportions of patients receiving etanercept had at least a 50% improvement in Ham-D or BDI at week 12 compared with the placebo group; patients treated with etanercept also had significant and clinically meaningful improvements in fatigue (mean FACIT-F improvement 5·0 vs 1·9; p<0·0001, difference 3·0, 95% CI 1·6–4·5). Improvements in fatigue were correlated with decreasing joint pain, whereas improvements in symptoms of depression were less correlated with objective measures of skin clearance or joint pain.

Interpretation

Etanercept treatment might relieve fatigue and symptoms of depression associated with this chronic disease.

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.

Section snippets

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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