Efficacy and safely of combination etanercept and methotrexate versus etanercept alone in patients with rheumatoid arthritis with an inadequate response to methotrexate: The ADORE study

Radboud University Nijmegen, Nymegen, Gelderland, Netherlands
Annals of the Rheumatic Diseases (Impact Factor: 10.38). 12/2006; 65(11):1478-83. DOI: 10.1136/ard.2005.043299
Source: PubMed


To evaluate the efficacy and safety of etanercept (ETN) monotherapy compared with combination ETN and methotrexate (MTX) treatment in patients with rheumatoid arthritis who had an inadequate response to MTX monotherapy. (The response was defined by the presence of Disease Activity Score-28 joint count (DAS28) >or=3.2 or a combination of >or=5 swollen joints, >or=5 painful joints and erythrocyte sedimentation rate >or=10 mm/h.)
Patients with active rheumatoid arthritis taking MTX >or=12.5 mg/week for >or=3 months were included in this 16 week, randomised, open-label study. Patients were randomly assigned to either ETN (25 mg subcutaneous injection twice weekly) added to the baseline dose of MTX or ETN monotherapy.
315 patients were randomised to ETN (n = 160) or ETN plus MTX (n = 155). The primary end point, DAS28 (4) improvement of >1.2 units, was achieved by 72.8% and 75.2% of patients treated with ETN and those treated with ETN plus MTX, respectively, with no significant difference (p = 0.658) between the two groups. The European League Against Rheumatism response criteria of good or moderate response was attained by 80.0% of patients in the ETN group and by 82.4% of patients in the ETN plus MTX group. American College of Rheumatology 20%, 50% and 70% response rates achieved by both groups were also similar: 71.0% v 67.1%, 41.9% v 40.1% and 17.4% v 18.4%, respectively. The rates of adverse and serious adverse events were similar between the treatment groups.
Both the addition of ETN to MTX and the substitution of ETN for MTX in patients with rheumatoid arthritis who had an inadequate response to MTX resulted in substantial improvements in clinical signs and symptoms and were generally well-tolerated treatment strategies for improving clinical signs and symptoms of rheumatoid arthritis.

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    • "Since antibodies to the anti-TNF-α antibodies decrease serum levels of the anti-TNF-α antibody and diminish the therapeutic effects [36-39], MTX combination is mandatory in treatments with infliximab, adalimumab, or golimumab. Of interest, TNF-α-receptor-Fc-fusion protein (etanercept) has been shown to be effective for RA even as a monotherapy because antibodies against etanercept are rarely produced [40]. However, a recent report has shown that, in MTX-refractory patients with RA, clinical response is better with etanercept plus MTX than with etanercept alone [41]. "
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    • "Previously, the combination of anti-TNF-α therapy and a cytotoxic drug has been shown to be superior to anti-TNF-α therapy alone [35]. However, this was not reported in all situations [36, 37]. In our patients, the immunosuppressive medication as taken at the start of anti-TNF-α therapy was continued unless side effects occurred or contra-indications existed. "
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    • "ETN was shown to be efficacious in more than 80% of the RA patients who were not successfully treated with prior DMARDs. Although other studies have reported that ETN is efficacious [7–13, 23–25], most of them involved relatively small numbers of patients so analysis of factors that can impact treatment outcome was either not possible or very limited. This study is unique in that it involved a large number of RA patients, allowing a more in-depth analysis of a variety of factors (e.g., duration of RA, functional class) with treatment outcome. "
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