Randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etanercept in patients with moderately active rheumatoid arthritis despite DMARD therapy

This study evaluated the efficacy and safety of adding etanercept to disease-modifying antirheumatic drugs (DMARDs) in patients with moderately active rheumatoid arthritis (RA). This randomized, double-blind, placebo-controlled study (ClinicalTrials.gov #NCT01313208) enrolled RA patients with Disease Activity Score using 28 joints with C-reactive protein (DAS28-CRP) > 3.2 and <= 5.1 (moderate disease) despite stable DMARD therapy. Patients were randomized to etanercept 50 mg or placebo weekly for 12 weeks; all patients then received etanercept 50 mg weekly through week 24. Primary endpoint was low disease activity (LDA) at week 12; secondary endpoints included DAS28-CRP remission at week 12; Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) LDA; American College of Rheumatology (ACR) responses; change in Health Assessment Questionnaire Disability Index (HAQ-DI), and safety. For 210 patients with moderate disease at screening, (104 placebo; 106 etanercept), only 58% still had moderate disease at baseline. At week 12, 33% on etanercept and 21% on placebo achieved LDA (P = 0.055); remission was achieved in 19% and 12%, respectively (P = 0.14). At week 12, ACR20, ACR50, and ACR70 responses were observed in 29%, 13%, and 1% respectively, in patients on placebo, and 41%, 21%, and 6% of patients on etanercept. Mean (SD) change from baseline in HAQ-DI score was -0.20 (0.43) for placebo patients and -0.39 (0.54) for etanercept patients at week 12. No new safety signals were observed. LDA was achieved by more patients on etanercept than placebo in patients with moderate disease at screening, but the difference was not statistically significant at week 12.