Elsevier

The Lancet

Volume 356, Issue 9227, 29 July 2000, Pages 385-390
The Lancet

Articles
Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial

https://doi.org/10.1016/S0140-6736(00)02530-7Get rights and content

Summary

Background

Etanercept, a tumour-necrosis-factor inhibitor, has shown efficacy in the treatment of rheumatoid arthritis. Psoriatic arthritis and psoriasis are disease states in which tumour necrosis factor, a proinflammatory cytokine, is present in increased concentrations in joints and in the skin. Therefore, psoriatic arthritis and psoriasis may be appropriate therapeutic targets for etanercept.

Methods

This randomised, double-blind, placebo-controlled, 12 week study assessed the efficacy and safety of etanercept (25 mg twice-weekly subcutaneous injections) or placebo in 60 patients with psoriatic arthritis and psoriasis. Psoriatic arthritis endpoints included the proportion of patients who met the Psoriatic Arthritis Response Criteria (PsARC) and who met the American College of Rheumatology preliminary criteria for improvement (ACR20). Psoriasis endpoints included improvement in the psoriasis area and severity index (PASI) and improvement in prospectively-identified individual target lesions.

Findings

In this 12 week study, 26 (87%) of etanercept-treated patients met the PsARC, compared with seven (23%) of placebo-controlled patients. The ARC20 was achieved by 22 (73%) of etanercept-treated patients compared with four (13%) of placebo-treated patients. Of the 19 patients in each treatment group who could be assessed for psoriasis (≥3% body surface area), five (26%) of etanercept-treated patients achieved a 75% improvement in the PASI, compared with none of the placebo-treated patients (p=0·015). The median PASI improvement was 46% in etanercept-treated patients versus 9% in placebo-treated patients; similarly, median target lesion improvements were 50% and O, respectively. Etanercept was well tolerated.

Interpretation

Etanercept offers patients with psoriatic arthritis and psoriasis a new therapeutic option for control of their disease.

Introduction

Commonly used topical therapies for skin lesions in psoriasis include moisturisers, corticosteroids, tar, anthralin, vitamin D analogues and retinoids, and ultraviolet-light therapy. When these therapies are inadequate, systemic therapies such as psoralen-ultraviolet-light treatment, methotrexate, ciclosporin, and acitretin may be used.1, 2 However, toxicities often limit the usefulness of these therapies.3, 4, 5

Psoriatic arthritis affects from 5% to 7% of patients with psoriasis.6 Although psoriatic arthritis may present in a symmetric polyarticular form similar to rheumatoid arthritis, unique features include the potential for asymmetric, oligoarticular, axial and/or distal interphalangeal joint involvement, dactylitis, and enthesial inflammation.7 Like rheumatoid arthritis, this disorder results in joint damage, disability, and increased mortality.8, 9, 10, 11

Therapy for psoriatic arthritis has largely been derived from clinical experience in rheumatoid arthritis, without corroborating evidence from studies in patients with psoriatic arthritis.12, 13, 14 The response to therapy is often unsatisfactory. The few controlled trials assessing patients with psoriatic arthritis have not shown consistent efficacy.15, 16, 17, 18, 19, 20

Etanercept functions by inhibiting tumour necrosis factor, a proinflammatory cytokine that is involved in many inflammatory disorders, including both psoriatic arthritis and psoriasis. Tumour necrosis factor has been shown to be increased in synovial fluid and synovium in patients with psoriatic arthritis and in the skin of psoriatic lesions.21, 22, 23, 24 Tumour-necrosis-factor inhibition with etanercept has previously been shown to diminish the activity of rheumatoid arthritis.25 Our study was undertaken to assess the benefit of etanercept in psoriatic arthritis and psoriasis.

Section snippets

Patients

Eligible patients were adults between 18 and 70 years who had active psoriatic arthritis (defined as ≥3 swollen joints and ≥3 tender or painful joints) at the time of study enrolment. Patients must have had an inadequate response to non-steroidal anti-inflammatory drugs and were thought candidates for immunomodulatory therapy. Patients taking methotrexate (≤25 mg/week) were allowed to continue methotrexate if the dose was stable for 4 weeks before study start and remained stable throughout the

Results

Table 1 shows baseline demographic and clinical characteristics. 60 patients were randomised, 30 in each treatment arm (figure 1). The median age was 45 years (range 24–70) and the median duration of psoriatic arthritis was 10 years (1–31). The median duration of psoriasis was 18 years (2–53) for all patients in the study and was 20 years (4–53) for the 38 patients with evaluable psoriasis (19 patients in each group). The median active joint counts at baseline were 20 tender and 14 swollen

Discussion

Few double-blind, placebo-controlled trials have been done in patients with psoriatic arthritis. Most therapies used to treat psoriatic arthritis have been attempted because they showed benefit in patients with rheumatoid arthritis or were therapies that yielded apparent benefit in open uncontrolled trials. The few controlled trials with patients with psoriatic arthritis have yielded inconsistent results.15, 16, 17, 18, 19, 20

Aside from non-steroidal anti-inflammatory agents, methotrexate has

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