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Methotrexate alone appears to be just as effective as methotrexate combined with Enbrel® (etanercept) in reducing tender and swollen joints in patients with early rheumatoid arthritis (RA) who have at least one joint with clinical synovitis, according to results from a study published in the Annals of the Rheumatic Diseases.

Initial treatment for RA often involves disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. Methotrexate may be used alone or in combination with other drugs.

Enbrel is a type of biologic disease-modifying antirheumatic drug (DMARD) known as a TNF inhibitor. TNF is a protein that contributes to the inflammation of RA and several other conditions, and Enbrel reduces the level of active TNF in the body.

This randomized, placebo-controlled trial included 110 patients with early clinical synovitis who had never been treated with a DMARD. Patients were randomized to receive methotrexate plus Enbrel or methotrexate plus placebo for 52 weeks. Patients with no tender of swollen joints (NTSJ) for 26 weeks or longer were able to stop receiving Enbrel injections early. If they still had NTSJ 12 weeks after stopping injections, they were weaned off methotrexate as well. The primary endpoint was NTSJ at week 52.

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The results indicated no statistically significant difference between the two groups for the primary endpoint or secondary endpoints. NTSJ at week 52 was 32.5 percent in the combination group and 28.1 percent in the methotrexate group. However, in exploratory analyses, a significantly higher proportion of patients in the combination therapy group achieved a 28-joint, DAS28-CRP of less than 2.6 at 2 weeks than did those taking methotrexate monotherapy (38.5% vs. 9.2%) as well as for DAS28-CRP of 3.2 or lower (55.5% vs. 22.2%).

The researchers concluded that methotrexate alone was equally as effective as methotrexate plus Enbrel in reducing tender and swollen joints in early RA; however, methotrexate plus Enbrel produced a more rapid clinical response.


Nam JL, Villeneuve E, Hensor EMA, et al: A randomized controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial. Annals of the Rheumatic Diseases.Published early online March 11, 2014. doi:10.1136/annrheumdis-2013-204882