PMID- 29259050 OWN - NLM STAT- MEDLINE DCOM- 20190122 LR - 20220330 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 77 IP - 4 DP - 2018 Apr TI - 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. PG - 488-494 LID - 10.1136/annrheumdis-2017-212172 [doi] AB - 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. CI - (c) 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. FAU - Matsuno, Hiroaki AU - Matsuno H AD - Matsuno Clinic for Rheumatic Diseases, Toyama, Japan. AD - Institute of Medical Science, Tokyo Medical University, Tokyo, Japan. FAU - Tomomitsu, Masato AU - Tomomitsu M AD - Mochida Pharmaceutical, Tokyo, Japan. FAU - Hagino, Atsushi AU - Hagino A AD - Mochida Pharmaceutical, Tokyo, Japan. FAU - Shin, Seonghye AU - Shin S AD - LG Chem, Seoul, Korea. FAU - Lee, Jiyoon AU - Lee J AD - LG Chem, Seoul, Korea. FAU - Song, Yeong Wook AU - Song YW AD - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Center, Seoul National University, Seoul, Korea. AD - Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, Korea. LA - eng SI - ClinicalTrials.gov/NCT02357069 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20171219 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antirheumatic Agents) RN - 0 (Biosimilar Pharmaceuticals) RN - 0 (Immunoglobulin G) RN - 0 (LBEC0101) RN - 0 (Receptors, Tumor Necrosis Factor) RN - OP401G7OJC (Etanercept) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adult MH - Aged MH - Antirheumatic Agents/pharmacokinetics/*therapeutic use MH - Arthritis, Rheumatoid/blood/*drug therapy MH - Biosimilar Pharmaceuticals/*therapeutic use MH - Blood Sedimentation MH - Double-Blind Method MH - Etanercept/pharmacokinetics/*therapeutic use MH - Female MH - Humans MH - Immunoglobulin G/metabolism/*therapeutic use MH - Least-Squares Analysis MH - Male MH - Methotrexate/therapeutic use MH - Middle Aged MH - Receptors, Tumor Necrosis Factor/metabolism/*therapeutic use MH - Severity of Illness Index MH - Therapeutic Equivalency MH - Treatment Outcome MH - Young Adult PMC - PMC5890628 OTO - NOTNLM OT - Das28 OT - Methotrexate OT - Rheumatoid Arthritis COIS- 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. EDAT- 2017/12/21 06:00 MHDA- 2019/01/23 06:00 PMCR- 2018/04/09 CRDT- 2017/12/21 06:00 PHST- 2017/08/02 00:00 [received] PHST- 2017/11/06 00:00 [revised] PHST- 2017/11/10 00:00 [accepted] PHST- 2017/12/21 06:00 [pubmed] PHST- 2019/01/23 06:00 [medline] PHST- 2017/12/21 06:00 [entrez] PHST- 2018/04/09 00:00 [pmc-release] AID - annrheumdis-2017-212172 [pii] AID - 10.1136/annrheumdis-2017-212172 [doi] PST - ppublish SO - Ann Rheum Dis. 2018 Apr;77(4):488-494. doi: 10.1136/annrheumdis-2017-212172. Epub 2017 Dec 19.