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Ann Rheum Dis. 2018;77(4):488-494.

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.

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제1저자 Hiroaki Matsuno · 교신저자 송영욱

PMID 29259050 PMC5890628 DOI 10.1136/annrheumdis-2017-212172 IF 24 류마티스내과
소속 (6)
  1. Matsuno Clinic for Rheumatic Diseases, Toyama, Japan.
  2. Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
  3. Mochida Pharmaceutical, Tokyo, Japan.
  4. LG Chem, Seoul, Korea.
  5. 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.
  6. Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, Korea.

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.

© 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.

Keywords

Das28MethotrexateRheumatoid Arthritis

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.

그림 출처: PubMed Central 공개 논문 (PMC5890628)

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.

그 밖의 정보
출판 형태
Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
저널
Annals of the rheumatic diseases · eISSN 1468-2060
전자 출판
2017-12-19
MeSH
Adult · Aged · Antirheumatic Agents / pharmacokinetics / therapeutic use · Arthritis, Rheumatoid / blood / drug therapy · Biosimilar Pharmaceuticals / therapeutic use · Blood Sedimentation · Double-Blind Method · Etanercept / pharmacokinetics / therapeutic use · Female · Humans · Immunoglobulin G / metabolism / therapeutic use · Least-Squares Analysis · Male · Methotrexate / therapeutic use · Middle Aged · Receptors, Tumor Necrosis Factor / metabolism / therapeutic use · Severity of Illness Index · Therapeutic Equivalency · Treatment Outcome · Young Adult
Substances
Antirheumatic Agents · Biosimilar Pharmaceuticals · Immunoglobulin G · LBEC0101 · Receptors, Tumor Necrosis Factor · Etanercept · Methotrexate
데이터
ClinicalTrials.gov: NCT02357069
참고문헌
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