Wyeth Pharmaceuticals, a division of Wyeth announced that the European Commission has approved Enbrel (25 mg twice weekly), for use in combination with methotrexate for the treatment of active rheumatoid arthritis (RA) in adults when the response to disease-modifying antirheumatic drugs (DMARDs) (including methotrexate unless contraindicated) has been inadequate. This new indication is in addition to the previously approved indication for use of Enbrel as monotherapy in the treatment of active RA.

This approval is based on one-year results from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO). In the study, RA patients treated with a combination of Enbrel and methotrexate demonstrated an improvement in X-ray findings as measured by the modified Total Sharp Score (TSS), and 80 percent of the patients experienced no progression of joint damage. Additionally, 37 per cent of RA patients treated with combination therapy achieved clinical remission as measured by Disease Activity Score (DAS) improvement, and 43 per cent experienced a 70 per cent improvement in RA symptoms as measured by American College of Rheumatology (ACR) response criteria.

In the TEMPO study, patients were assigned to one of three treatment groups: Enbrel (25 mg twice weekly), methotrexate (up to 20 mg once weekly), or Enbrel (25 mg twice weekly) plus methotrexate. Progression of joint damage was evaluated using the modified TSS, an X-ray measurement of changes in joint damage. Patients receiving combination treatment with Enbrel and methotrexate achieved a mean improvement of -0.54 in the modified TSS compared to baseline. Eighty percent of patients in the combination group showed "no progression," which was defined as a change in modified TSS <0.5. In comparison, 68 per cent and 57 per cent of Enbrel monotherapy and methotrexate monotherapy-treated patients, respectively, had no progression of joint damage at one year.

In the study, 37 per cent of patients receiving Enbrel and methotrexate in combination achieved clinical remission at one year, which was defined as a DAS of less than 1.6. In comparison, 18 per cent of patients treated with Enbrel alone and 14 per cent of patients treated with methotrexate alone achieved clinical remission during the same time period. The DAS incorporates the number of tender and swollen joints, erythrocyte sedimentation rate (ESR, a marker of inflammation), and general health assessment.

Efficacy was also evaluated using ACR response criteria, a composite measure of improvement in RA symptoms, including the number of tender and swollen joints, pain, level of disability, overall self- and physician assessment, and an objective marker of inflammation, such as ESR or C-reactive protein. The ACR response is defined by the level of improvement - 20 per cent, 50 per cent, or 70 per cent - where 70 per cent describes an improvement that is greatest in degree and, therefore, most clinically meaningful. At one year, 43 per cent of patients in the combination therapy group experienced a 70 per cent improvement in ACR score, while 24 per cent of patients treated with Enbrel alone and 19 per cent of patients treated with methotrexate alone achieved the same improvement.

"The data we've seen from the TEMPO trial - using Enbrel either alone or in combination with methotrexate for the treatment of RA - is truly exciting, offering many patients the option for effective treatment and possibly preventing radiographic progression in RA," says Dr. Joseph Camardo, senior vice president, Global Medical Affairs, Wyeth Pharmaceuticals.

"Enbrel has a history of proven efficacy and tolerability in RA, and new information gathered through clinical trials such as TEMPO allows us to explore new treatment options to help improve the lives of RA patients," says Dr. Magnus Jaderberg, vice president of Global Medical Affairs and European Medical Director of Wyeth Pharmaceuticals. "We will also see the clinical two-year results from the TEMPO study presented at the European League Against Rheumatism (EULAR) congress in June, which will provide even more information that can help physicians make important treatment decisions for their RA patients."