• Rheumatoid Arthritis Clinical Trials

• Rheumatology
• Rheumatoid Arthritis
• Rheumatology Clinical Trials

The new agent HD203 is a biosimilar of etanercept, a recombinant fusion protein that blocks tumor necrosis factor activity. The amino acid sequence of HD203 is identical to that of etanercept and is produced by the same method. A Phase 1 trial in healthy volunteers indicated that the pharmacokinetics, safety, and tolerability of HD203 were comparable to those of etanercept [Yi S et al. BioDrugs 2012].

The objective of the Trial to Evaluate Equivalence in Efficacy and Safety of HD203 and Enbrel in RA Patients [HERA; NCT01270997], presented by Sang-Cheol Bae, MD, PhD, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, was to evaluate the equivalence in efficacy of HD203 and etanercept in combination with methotrexate in patients with rheumatoid arthritis (RA). The patients were randomly assigned to HD203 (25 mg; n=115) or etanercept (25 mg; n=118), subcutaneous injection, twice weekly, for 24 weeks. An extension study continued for an additional 24 weeks.

The inclusion criteria included fulfillment of 1987 American College of Radiology (ACR) criteria for RA; class I to III ACR functional status; active RA; positive rheumatoid factor, anti-CCP antibody, or bone erosion in the hands or feet; and inadequate response to methotrexate. The primary efficacy endpoint was the ACR20 score, assessed at Week 24. The secondary endpoints were ACR20, ACR50, and ACR70, assessed at Weeks 12, 24, and 48, and the index of improvement in RA, Disease Activity Score in 28 joints (DAS28), and European League Against Rheumatism (EULAR) response, assessed at Weeks 24 and 48. Efficacy equivalence was defined as a 95% CI between the 2 drugs of −20% to +20%.

The mean patient age was ∼51 years in each group, and 85.6% to 87.8% of patients were women. ACR functional status was similar between the 2 groups. The primary endpoint of ACR20 at Week 24 was achieved by 83.48% of patients in the HD203 group, compared with 81.36% of patients in the etanercept group (95% CI, 7.65 to 11.89; p=0.6706).

There were no significant differences between the groups in the percentage of patients achieving ACR20 at Weeks 12 and 48; ACR50 at Week 12; and ACR70 at Weeks 12, 24, and 48 (Table 1). A significant difference was observed for ACR50 in the HD203 group versus the etanercept group at Weeks 24 (65.2% vs 52.5%; p=0.0494) and 48 (68.2% vs 54.5%; p=0.0359).

At Weeks 24 and 48, there were no significant differences between the groups in mean change in DAS28 (Week 24, p=0.9170; Week 48, p=0.2534) or EULAR response rate (Week 24, p=0.5991; Week 48, p=0.1264).

The adverse event (AE) rate at 48 weeks was 76.9% in the HD203 group and 78.1% in the etanercept group. Serious AEs were reported in 12.9% of HD203 patients and 12.3% of etanercept patients. The withdrawal rate was 6.8% in the HD203 group and 7.5% in the etanercept group. Ten patients in the HD203 group and 4 in the etanercept group developed transient antidrug antibodies over 48 weeks.

This study demonstrated the equivalent efficacy and comparable safety of HD203 and etanercept in patients with RA. These findings confirm the biosimilarity of the 2 drugs.

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