Background: Etanercept is a recombinant fusion protein that blocks TNF. HD203 is a biosimilar of etanercept with demonstrated comparability across pharmacokinetics, safety and tolerability. The objectives of this study were to evaluate equivalence in effi cacy and compare safety of HD203 with reference etanercept, in combination with MTX in patients with RA. (ClinicalTrials. gov NCT01270997). Methods: Korean patients (male or female aged =20 years) with active RA were randomized (1:1) to 25 mg HD203 or reference etanercept, administered subcutaneously twice weekly with MTX for 48 weeks. The primary endpoint was the proportion of patients achieving ACR20 at week 24. Secondary endpoints included ACRn, DAS28, andEULAR response at week 24 and 48, safety and immunogenicity. Results: In total, 294 patients were randomized: HD203, n=147; reference etanercept, n=147. The proportion of patients achieving ACR20 at week 24 was not signifi cantly different between HD203 and reference etanercept. Equivalent effi cacy was demonstrated within predefined margins. There were no significant differences between proportions achieving ACR20 at week 12 and 48. ACR50 and ACR70 displayed similar trends. There were no signifi cant differences between groups for ACRn, DAS28, and EULAR response. Safety set analysis (HD203, n=147; reference etanercept, n=146) revealed no signifi cant difference for treatment-emergent (all-causality) adverse events (AEs): HD203 76. 87% vs. reference etanercept 78. 08% (p=0. 8040). No significant differences between HD203 and reference etanercept were observed for adverse drug reactions, serious AEs, or discontinuations due to AEs. Few patients tested positive for anti-drug antibodies. Conclusions: The study met the primary endpoint of demonstrating equivalent effi cacy of HD203 compared to reference etanercept. HD203 was well tolerated, with a safety profi le comparable to reference etanercept in this population of patients with RA.