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Etanercept

A Review of its Use in Rheumatoid Arthritis

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Summary

Abstract

Etanercept, a fusion protein consisting of the extracellular ligand-binding domain of the 75kD receptor for tumour necrosis factor-α and the constant portion of human IgG1, is administered by subcutaneous injection and is the first specific anti-cytokine therapy approved for rheumatoid arthritis.

In patients with active rheumatoid arthritis [American College of Rheumatology (ACR) functional class I to III] who had failed to respond to previous treatment with ≥1 disease-modifying antirheumatic drug (DMARD), etanercept, alone or in combination with methotrexate, produced improvements in all components included in the ACR core set of disease activity measures.

A dose-response effect was apparent with etanercept 0.25 to 16 mg/m2 twice weekly in a randomised, double-blind study in 180 patients. The mean number of swollen or tender joints at the end of the 12-week study decreased by >50% in patients treated with etanercept 16 mg/m2 twice weekly and by >25% in patients treated with placebo.

In a 24-week multicentre, randomised, double-blind study in 234 patients who were not allowed to use DMARDs, etanercept 10 or 25mg twice weekly had a rapid onset of effect. Significantly more patients treated with etanercept 25mg twice weekly than placebo experienced 20 (ACR 20), 50 (ACR 50) or 70% (ACR 70) improvement in ACR criteria after 3 and 6 months. Limited evidence suggests that the therapeutic effects of etanercept are maintained for up to 2 years.

Etanercept 25mg twice weekly produced significant improvement in patients receiving oral or subcutaneous methotrexate 10 to 25 mg/week in a multicentre, randomised, double-blind, placebo-controlled study. A significantly greater proportion of patients treated with etanercept plus methotrexate (71%) than placebo plus methotrexate (27%) achieved the ACR 20 criteria after 6 months. Moreover, 39 and 15% of patients treated with etanercept plus methotrexate, but no placebo plus methotrexate recipients, had achieved the ACR 50 and ACR 70 criteria at this time.

Etanercept 0.4 mg/kg twice weekly reduced disease activity in a preliminary, noncomparative study in 69 children aged ≥4 years with refractory juvenile rheumatoid arthritis.

Although the overall frequency of infections was similar in patients treated with etanercept or placebo, upper respiratory tract infections were more common in patients treated with etanercept (29%) than placebo (16%). Injection site reactions occurred more frequently in etanercept-than placebo-treated patients, but did not bias the results of any study.

Conclusions: When etanercept is administered alone or in combination with methotrexate in patients with refractory rheumatoid arthritis, significant reductions in disease activity occur within 2 weeks and are sustained for at least 6 months. Thus, etanercept appears to be particularly well suited for use in patients who fail to respond to treatment with DMARDs.

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Correspondence to Blair Jarvis.

Additional information

Various sections of the manuscript reviewed by: A.P. Cope, The Kennedy Institute of Rheumatology, Immunology Division, London, England; B. Deleuran, Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; M. Dougados, Clinique de Rheumatologie, Hôpital Cochin, Paris, France; A. Eigler, Medizinische Klinik, Klinikum Innenstadt der Ludwig Maximilians Universität, Munich, Germany; S. Endres, Medizinische Klinik, Klinikum Innenstadt der Ludwig Maximilians Universität, Munich, Germany; G.S. Firestein, Division of Rheumatology, Allergy and Immunology, University of California at San Diego School of Medicine, La Jolla, California, USA; Ø. Førre, Rikshospitalet, The National Hospital, University of Oslo, Oslo, Norway; D.J. Lovell, Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA; M. Østergaard, Department of Rheumatology, Hvidovre Hospital, Hvidovre, Denmark; M. Swims, Department of Pharmacy Practice and Pharmacoeconomics, College of Pharmacy, University of Tennessee, and Veterans Affairs Medical Center, Memphis, Tennessee, USA.

Data Selection

Sources: Medical literature published in any language since 1966 on etanercept, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand), Medline and EMBASE. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase search terms were ‘etanercept’, ‘enbrel’, ‘TNF-001’ and ‘TNFR-Fc’. Medline and EMBASE search terms were ‘etanercept’, ‘enbrel’, ‘TNF-001’ and ‘TNFR-Fc’. Searches were last updated 10 May, 1999.

Selection: Studies in patients with rheumatoid arthritis who received etanercept. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: etanercept, pharmacodynamics, pharmacokinetics, rheumatoid arthritis, therapeutic use.

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Jarvis, B., Faulds, D. Etanercept. Drugs 57, 945–966 (1999). https://doi.org/10.2165/00003495-199957060-00014

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