Objective: To evaluate the efficacy and safety of treatment with 50 mg of etanercept twice a week plus weekly methotrexate (MTX; > or =15 mg) in patients with rheumatoid arthritis (RA) who had a suboptimal response to 50 mg of etanercept once a week plus weekly MTX (> or =15 mg).
Methods: In this multicenter, randomized, double-blind, active drug-controlled study, suboptimal responders to treatment with MTX plus etanercept 50 mg once weekly were given MTX plus etanercept 50 mg twice weekly (n = 160) or MTX plus etanercept 50 mg once weekly plus a placebo (n = 40) for 12 weeks. In a subsequent 12-week open-label period, patients who responded to etanercept 50 mg twice weekly decreased their dosage to 50 mg once weekly, those who had a partial response to etanercept 50 mg once weekly increased their dosage to 50 mg twice weekly, and those who had no response to etanercept 50 mg twice weekly were discontinued. The primary end point was the proportion of patients with a response on the Disease Activity Score 28-joint assessment (DAS28) at week 12.
Results: A total of 201 patients were randomized; 187 completed 12 weeks, and 102 completed 24 weeks. At week 12 (double-blind period), the DAS28 response in the 50 mg twice weekly and the 50 mg once weekly groups was not significantly different (45.6% versus 35.0%; P = 0.285), and similar proportions of patients in the groups taking 100 mg and 50 mg experienced adverse events (34.4% versus 37.5%; P = 0.711). Serious adverse events occurred in 7 of 160 of the 50 mg twice weekly group and 0 of 40 of the 50 mg once weekly group (P = 0.387), and serious infectious events occurred in 3 of 160 patients in the 50 mg twice weekly group (P = 0.884).
Conclusion: Etanercept 50 mg once weekly is an optimal dosage in most patients with RA. Increasing the dosage from 50 mg once weekly to 50 mg twice weekly in suboptimal responders did not significantly improve their DAS28 responses.
Trial registration: ClinicalTrials.gov NCT00115219.