Switch from reference etanercept to SDZ ETN, an etanercept biosimilar, does not impact efficacy, safety, and immunogenicity of etanercept in patients with moderate-to-severe rheumatoid arthritis: 48-week results from the phase III, randomized, double-blind EQUIRA study

Abstract

Background Sandoz etanercept (SDZ ETN; GP2015) is an etanercept biosimilar with equivalent efficacy and comparable safety and immunogenicity to reference etanercept (ETN) in patients with moderate-to-severe chronic plaque-type psoriasis. Methods EQUIRA was a phase III, double-blind study conducted in patients with moderate-to-severe rheumatoid arthritis and inadequate response to disease-modifying anti-rheumatic drugs. Eligible patients were randomized 1:1 to receive subcutaneous 50 mg SDZ ETN or ETN, once-weekly, for 24 weeks. At week 24, patients with at least moderate EULAR response in the SDZ ETN group continued SDZ ETN treatment, and those in the ETN group were switched to receive 50 mg SDZ ETN, for up to 48 weeks. Patients received concomitant methotrexate at a stable dose (10–25 mg/week) and folic acid (≥ 5 mg/week). Equivalence between SDZ ETN and ETN for change from baseline in disease activity score including 28 joint count C-reactive protein (DAS28-CRP) at week 24 (primary endpoint) and comparable safety and immunogenicity profile of SDZ ETN and ETN have previously been demonstrated at week 24. Herein, we present the 48-week results of the study after a single switch from ETN to its biosimilar at week 24. Results The least squares mean (standard error) change in DAS28-CRP from baseline up to week 48 was comparable between “continued SDZ ETN” (− 2.90 [0.12], n = 148) and “switched to SDZ ETN” (− 2.78 [0.13], n = 131) groups. The proportion of patients achieving EULAR good/moderate responses based on DAS28-erythrocyte sedimentation rate and ACR20/50/70 response rates were comparable between the two groups. The proportion of patients with at least one treatment-emergent adverse event was 42.9% in the “continued SDZ ETN” and 38.0% in the “switched to SDZ ETN” groups. Serious adverse events occurred in 4 patients in each of the two groups. After week 24, none of the patients in the switched group developed anti-drug antibodies (ADAs), while 4 patients in the continued SDZ ETN group had single-event, very low titer, non-neutralizing ADAs detected. Conclusions The 48-week results from the EQUIRA study demonstrate that switch from ETN to SDZ ETN in patients with moderate-to-severe rheumatoid arthritis does not impact the efficacy, safety, or immunogenicity of etanercept. Trial registration EudraCT number 2012-002009-23 , Registered 19 April 2012—prospectively registered. Electronic supplementary material The online version of this article (10.1186/s13075-019-1907-x) contains supplementary material, which is available to authorized users.

Patient-Reported Outcomes in Rheumatoid Arthritis: A Key Consideration for Evaluating Biosimilar Uptake?

“…The improvement with GP2017 was maintained after switching at week 48. 50 In the EQUIRA study, the mean change from baseline in the FACIT-fatigue score at week 24 was 9.45 in the biosimilar GP2015 group and 11.82 in the etanercept group. Furthermore, no difference in FACIT-fatigue score was reported after switching to GP2015.…”

“…The EQUIRA study 50 , 54 aimed demonstrated similar efficacy and comparable safety and immunogenicity profile of GP2015 (Erelzi ® ; Sandoz GmbH, Kundl, Austria) to etanercept (Enbrel ® ; Immunex Corporation, Thousand Oaks, CA, USA) at week 24 in patients with moderate-to-severe RA who had an inadequate response to either synthetic or biologic DMARDs. Improvements from baseline in HAQ-DI and scores were comparable between GP2015 and etanercept groups.…”

“…Furthermore, the proportion of patients achieving HAQ-DI ≤0.5 up to week 48 was comparable between “continued GP2015” group and “switched to GP2015” group (34.7% vs 39.5%). 50 …”

“… 65 The knowledge of real-world clinical use of approved biosimilars would help assess the effectiveness, safety, and QoL of biosimilars in the treatment of RA. 50 However, lack of randomization makes observational effect estimates vulnerable to confounding. 66 …”

LBEC0101, an etanercept biosimilar for the treatment of rheumatoid arthritis

“…Biosimilar drugs can be approved for use in all indications held by the originator biologic by extrapolation of efficacy and safety data from at least one indication of the originator and with adequate scientific justification, that is, without direct comparative clinical studies in all indications [22]. Regarding switching from an originator product to a biosimilar, numerous published biosimilar studies have reported no safety or efficacy concerns even though not all regulatory guidelines require collection of such data [23][24][25][26][27].…”