Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study

Min-Chan Park, Hiroaki Matsuno, Jinseok Kim, Sung-Hwan Park, Sang-Heon Lee, Yong-Beom Park, Yun Jong Lee, Sang-Il Lee, Won Park, Dong Hyuk Sheen, Jung-Yoon Choe, Chan-Bum Choi, Seung-Jae Hong, Chang-Hee Suh, Shin-Seok Lee, Hoon-Suk Cha, Bin Yoo, Jin-Wuk Hur, Geun-Tae Kim, Wan-Hee Yoo, Han Joo Baek, Kichul Shin, Seung Cheol Shim, Hyung-In Yang, Hyun Ah Kim, Kyung-Su Park, In Ah Choi, Jisoo Lee, Masato Tomomitsu, Seonghye Shin, Jiyoon Lee, Yeong Wook Song, Min-Chan Park, Hiroaki Matsuno, Jinseok Kim, Sung-Hwan Park, Sang-Heon Lee, Yong-Beom Park, Yun Jong Lee, Sang-Il Lee, Won Park, Dong Hyuk Sheen, Jung-Yoon Choe, Chan-Bum Choi, Seung-Jae Hong, Chang-Hee Suh, Shin-Seok Lee, Hoon-Suk Cha, Bin Yoo, Jin-Wuk Hur, Geun-Tae Kim, Wan-Hee Yoo, Han Joo Baek, Kichul Shin, Seung Cheol Shim, Hyung-In Yang, Hyun Ah Kim, Kyung-Su Park, In Ah Choi, Jisoo Lee, Masato Tomomitsu, Seonghye Shin, Jiyoon Lee, Yeong Wook Song

Abstract

Background: To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA).

Methods: This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100.

Results: A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively).

Conclusions: Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101.

Trial registration: ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.

Keywords: Biosimilar; Etanercept; LBEC0101; Rheumatoid arthritis; Switch.

Conflict of interest statement

HM has received consulting fees for this study from Mochida Pharmaceutical Co., Ltd.; consulting fees from AYUMI Pharmaceutical Corporation and Nichi-Iko Pharmaceutical Co., Ltd.; and lecture fees from Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd., outside of this study. MT is an employee of Mochida Pharmaceutical Co., Ltd. SS and JY are employees of LG Chem, Ltd. All authors other than HM, MT, SS and JY received grants for this extension study from LG Chem, Ltd.

Figures

Fig. 1
Fig. 1
Patient flow chart: Randomisation was carried out in the initial randomised trial only (1:1 ratio to LBEC0101 or ETN-RP), and no further randomisation was carried out in the extension study. *The number of patients enrolled in the extension study is different from the number finishing the phase III study because only Korean patients were enrolled in the extension study. ETN-RP, etanercept reference product
Fig. 2
Fig. 2
Disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) (full-analysis set). DAS28-ESR mean values at weeks 0, 52, 76 and 100. SE, standard error
Fig. 3
Fig. 3
ACR response rates (full-analysis set). a ACR20, b ACR50 and c ACR70 response rates at weeks 52, 76 and 100. ACR, American College of Rheumatology; CI, confidence interval
Fig. 4
Fig. 4
EULAR response rates (full analysis set). EULAR response rates at weeks 52, 76 and 100. EULAR, European League Against Rheumatism

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