Three Studies Document Switches to Biosimilar Etanercept

At the European League Against Rheumatism (EULAR)'s Annual European Congress of Rheumatology, researchers presented findings on 3 studies in which patients switched to a biosimilar etanercept molecule from the reference Enbrel.

Safety and efficacy of LBEC0101 similar in patients who switch and maintain treatment

LG Life Sciences’ LBEC0101 was the subject of a recent open-label extension period of a phase 3 study versus reference etanercept.¹ The extension period evaluated the long-term efficacy, safety, and immunogenicity of switching from the reference to LBEC0101 versus continuous treatment with LBEC0101 in patients with rheumatoid arthritis (RA).

Of the 148 patients enrolled in the study, 70 continued to receive the biosimilar and 78 patients switched from the reference. Data were analyzed for patients who received the biosimilar for 100 weeks and for those who received reference etanercept for 52 weeks followed by the biosimilar for 48 weeks.

Disease activity score measured in 28 joints (DAS28) with erythrocyte sedimentation rate (DAS28-ESR) in both groups was maintained from week 52. At week 100, response rates, according to American College of Rheumatology standards for 20% improvement (ACR20), were 79.7% in the maintenance group and 83.3% in the switch group. The percentage of patients achieving ACR50 in each group were 65.2% and 66.7%, respectively, and the percentage of patients achieving ACR70 in each group were 44.9% and 42.3%, respectively.

The incidence of adverse events (AEs) was comparable between the groups, at 70.0% for maintenance group and 70.5% for the switch group. The percentage of patients who developed anti-drug antibodies (ADAs) was also similar, with 1.4% of patients in the maintenance group and 1.3% of patients in the switch group developing ADAs.

A switch to GP2015 did not impact safety or efficacy

Another study reported on Sandoz’s proposed etanercept biosimilar, GP2015, in patients with RA who had an inadequate response to methotrexate.² The EQUIRA study was a 48-week, randomized, double-blind, phase 3 study with the primary endpoint of change from baseline in DAS28 with C-reactive protein (CRP).

Patients were randomized to receive GP2015 or the reference subcutaneously each week for 24 weeks, and patients with at least 1 moderate EULAR response either continued to receive the biosimilar or, in the reference group, switched to the biosimilar for up to 48 weeks. All patients continued to receive methotrexate at a stable dose.

The mean change in DAS28-CRP was comparable between groups through week 48. EULAR and ACR response rates were also comparable at week 48, with the percentage of patients in the maintenance and switch groups reaching the following:

• EULAR good response: 54.4%, 51.9%
• ACR20: 89.1%, 82.4%
• ACR50: 63.3%, 65.6%
• ACR70: 36.7%, 42.0%

AEs occurred in 42.9% and 38.0% of patients in the maintenance and switched groups, respectively, and serious AEs occurred in 2.3% and 2.4% of patients.

Nonmandatory switch to SB4 results in higher risk of discontinuation

Given the importance of shared decision-making in treating rheumatic diseases, nonmandatory switches may be preferable to mandatory ones. Researchers presented findings from a nonmandatory switch from reference etanercept to Samsung Bioepis’ SB4 in a cohort of 642 patients with inflammatory diseases.³

In 2016, the patients were asked to switch to the biosimilar via a structured communication strategy that included an opt-out option. In total, 635 (99%) patients agreed to the switch. A historical cohort of 600 patients, treated with reference etanercept in 2014, was used for comparison.

Crude 6-month retention rates for SB4 in the switch cohort and reference etanercept in the historical cohort were 90% (95% CI, 88%-93%) and 92% (95% CI, 90%-94%). The transition cohort had a significantly higher relative risk of discontinuation, with an adjusted hazard ratio of 1.57 (95% CI, 1.05-2.36).

Those who switched also had a smaller decrease from baseline in CRP, with an adjusted difference of 1.8 (95% CI, 0.3-3.2) and DAS28-CRP, with an adjusted difference of 0.15 (95% CI, 0.05-0.25) at 6 months. The authors of the study say that these differences were not considered clinically relevant.

Since mandatory switching is unlikely to be acceptable in many countries, write the authors, using a communication strategy that optimizes acceptance may help to improve persistence rates in those switched to biosimilars.

References

1. Song YW, Matsuno H, Park M-C, Tomomitsu M, Shin S, Lee J. Efficacy and safety of switching from etanercept reference product to LBEC0101 (etanercept biosimilar) compared with continuing LBEC0101 in patients with rheumatoid arthritis. Presented at the European League Against Rheumatism’s Annual European Congress of Rheumatology, June 13-16, 2018; Amsterdam, Netherlands. Abstract AB0456. 10.1136/annrheumdis-2018-eular.1316

2. Matucci-Cerinic M, Schulze-Koops H, Buch M, et al. Switch between reference etanercept (ETN) and GP2015, an etanercept biosimilar, did not impact efficacy and safety in patients with modearate-to-severe rheumatoid arthritis: 48-week results from the phase 3 EQUIRA study. Presented at the European League Against Rheumatism’s Annual European Congress of Rheumatology, June 13-16, 2018; Amsterdam, Netherlands. Abstract FRI0129. doi: 10.1136/annrheumdis-2018-eular.1368.

3. Tweehuysen L, Huiskes VJB, van den Bemt BJF, et al. Open-label non-mandatory transitioning from originator etanercept to biosimilar SB4: 6-month results from a controlled cohort study. Presented at the European League Against Rheumatism’s Annual European Congress of Rheumatology, June 13-16, 2018; Amsterdam, Netherlands. Abstract FRI0127. doi: 10.1136/annrheumdis-2018-eular.2592.