Phase III, multicentre, double-blind, randomised, parallel-group study to evaluate the similarities between LBEC0101 and etanercept reference product in terms of efficacy and safety in patients with active rheumatoid arthritis inadequately responding to methotrexate

Hiroaki Matsuno, Masato Tomomitsu, Atsushi Hagino, Seonghye Shin, Jiyoon Lee, Yeong Wook Song, Hiroaki Matsuno, Masato Tomomitsu, Atsushi Hagino, Seonghye Shin, Jiyoon Lee, Yeong Wook Song

Abstract

Objective: To evaluate the similarities between LBEC0101 (etanercept biosimilar) and the etanercept reference product (ETN-RP) in terms of efficacy and safety, including immunogenicity, in patients with active rheumatoid arthritis despite methotrexate treatment.

Methods: This phase III, multicentre, randomised, double-blind, parallel-group, 54-week study was conducted in Japan and Korea. The primary efficacy endpoint was the change from baseline in the disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at week 24. American College of Rheumatology 20% (ACR20) response rate, adverse events (AEs), pharmacokinetics and development of antidrug antibodies (ADAs) were also evaluated.

Results: In total, 374 patients were randomised to LBEC0101 (n=187) or ETN-RP (n=187). The least squares mean changes from baseline in DAS28-ESR at week 24 in the per-protocol set were -3.01 (95% CI -3.198 to -2.820) in the LBEC0101 group and -2.86 (95% CI -3.051 to -2.667) in the ETN-RP group. The estimated between-group difference was -0.15 and its 95% CI was -0.377 to 0.078, which was within the prespecified equivalence margin of -0.6 to 0.6. ACR20 response rates at week 24 were similar between the groups (LBEC0101 93.3% vs ETN-RP 86.7%). The incidence of AEs up to week 54 was comparable between the groups (LBEC0101 92.0% vs ETN-RP 92.5%), although fewer patients in the LBEC0101 group (1.6%) than the ETN-RP group (9.6%) developed ADAs.

Conclusion: The clinical efficacy of LBEC0101 was equivalent to that of ETN-RP. LBEC0101 was well tolerated and had a comparable safety profile to ETN-RP.

Trial registration number: NCT02357069.

Keywords: Das28; Methotrexate; Rheumatoid Arthritis.

Conflict of interest statement

Competing interests: HM has received consulting fees for this study from Mochida Pharmaceutical, consulting fees unrelated to this study from AYUMI Pharmaceutical Corporation, Nichi-Iko Pharmaceutical and Meiji Seika Pharma, and lecture fees from Daiichi Sankyo, UCB Japan, Janssen Pharmaceutical KK, Chugai Pharmaceutical and Ono Pharmaceutical. MT and AH are employees of Mochida Pharmaceutical. SS and JL are employees of LG Chem. YWS received a grant for this study from LG Chem.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Patient disposition. A total of 517 patients were screened and 374 patients were randomised. Almost equal numbers of patients in Japan and Korea were allocated to each treatment group. Period I and period II mean weeks 0–24 and weeks 24–52, respectively. AEs, adverse events; ETN-RP, etanercept reference product.
Figure 2
Figure 2
DAS28-ESR change from baseline. (A) LS mean change from baseline in DAS28-ESR at week 24 and its 95% CI adjusted for the country of the study centre, status of previous use of a biological disease-modifying antirheumatic drugs and DAS28-ESR at baseline (PPS-24w and FAS). (B) Mean±SD of DAS28-ESR at baseline, week 12, week 24 and week 52 (FAS). DAS28-ESR, disease activity score in 28 joints based on erythrocyte sedimentation rate; ETN-RP, etanercept reference product; FAS, full analysis set; LS, least squares; PPS-24w, per-protocol set for data up to week 24.
Figure 3
Figure 3
ACR20 (A), ACR50 (B), and ACR70 (C) response rates at weeks 12 and 24 (PPS-24w) and at week 52 (PPS-52w). ACR, American College of Rheumatology; ETN-RP, etanercept reference product; PPS-24w, per-protocol set at 24 weeks; PPS-52w, per-protocol set at 52 weeks.
Figure 4
Figure 4
EULAR response at weeks 12 and 24 (PPS-24w) and at week 52 (PPS-52w) ETN-RP, etanercept reference product; EULAR, European League Against Rheumatism; PPS-24w, per-protocol set at 24 weeks; PPS-52w, per-protocol set at 52 weeks.

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