Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial Hideto KamedaYukitaka UekiKazuyoshi SaitoShouhei NagaokaToshihiko Hidaka • Tatsuya AtsumiMichishi TsukanoTsuyoshi KasamaShunichi ShiozawaYoshiya Tanaka • Tsutomu TakeuchiJapan Biological Agent Study Integrated Consortium (JBASIC)

The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX- naive patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the com- mencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6-8 mg/week (the E ? M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demo- graphic and clinical features between groups at baseline were similar. The EULAR good response rates were sig- nificantly higher in the E ? M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E ? M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E ? M group (90%) than in the E group (64%; p = 0.0002). Safety pro- files were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX.