To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed.
Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals.
A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P < 0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P < 0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P < 0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P < 0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups.
Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.