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

Abstract

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.

Keywords: Etanercept; Randomized controlled trial; Rheumatoid arthritis.

Figure 1

Patient disposition. *One patient was counted as having both completed etanercept and discontinuing etanercept. The patient received all 12 doses of etanercept during weeks 1 through 12 of the study, but ended treatment on the day of the last dose because of an adverse event that required protocol-prohibited treatments.

Figure 2

Rates of DAS28-CRP LDA and remission. The percentages of patients with DAS28-CRP < 3.2 (LDA; top panels) and < 2.6 (remission; bottom panels) are shown. Data are shown for the primary analysis set (left panels) and the subset of patients with moderate RA at baseline (right panels). Patients in the placebo-etanercept group (black bars in left panels; gray bars in right panels) received placebo (hashed bars) in the first 12 weeks and etanercept through week 24 and patients in the etanercept-etanercept group received etanercept (gray bars in left panels; white bars in right panels) throughout the study. *P < 0.05; ^† P < 0.01; ^‡ P < 0.001 for comparison between groups. DAS28-CRP: Disease Activity Score based on 28 joints with C-reactive protein; LDA: low disease activity; RA: rheumatoid arthritis.

Figure 3

DAS28-CRP values. Mean DAS28-CRP values are shown for the placebo-etanercept (circles) and etanercept-etanercept (squares) groups. Dotted lines indicate the period when the placebo-etanercept group received placebo. Error bars represent standard deviations. *P < 0.05; ^† P < 0.01 for comparison between groups. DAS28-CRP: Disease Activity Score based on 28 joints with C-reactive protein; SD, standard deviation.