Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis - The ANSWER cohort study

Ebina, Kosuke; Hashimoto, Motomu; Yamamoto, Wataru; Hirano, Toru; Hara, Ryota; Katayama, Masaki; Onishi, Akira; Nagai, Koji; Son, Yonsu; Amuro, Hideki; Yamamoto, Keiichi; Maeda, Yuichi; Murata, Koichi; Jinno, Sadao; Takeuchi, Tohru; Hirao, Makoto; Kumanogoh, Atsushi; Yoshikawa, Hideki

doi:https://doi.org/10.1186/s13075-019-1880-4

Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis - The ANSWER cohort study

Ebina, Kosuke; Hashimoto, Motomu; Yamamoto, Wataru et al.

Arthritis Research and Therapy, 2019, 21(1), 91

Number of Access:2,628（2025-09-03 11:38 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93210

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Title	Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis - The ANSWER cohort study
Creator	NRID 1000070612076 1000070612076 researchmap permalink k-ebina k-ebina Scopus Author ID 8415453300 8415453300 ORCID 0000-0002-2426-1024 0000-0002-2426-1024 CreatorName Ebina, Kosuke
	NRID 1000060512845 1000060512845 CreatorName Hashimoto, Motomu
	CreatorName Yamamoto, Wataru
	CreatorName Hirano, Toru
	NRID 1000010597107 1000010597107 CreatorName Hara, Ryota
	CreatorName Katayama, Masaki
	NRID 1000060634269 1000060634269 CreatorName Onishi, Akira
	NRID 1000030572458 1000030572458 CreatorName Nagai, Koji
	CreatorName Son, Yonsu
	CreatorName Amuro, Hideki
	CreatorName Yamamoto, Keiichi
	NRID 1000010815658 1000010815658 Scopus Author ID 56655338200 56655338200 CreatorName Maeda, Yuichi
	NRID 1000060806793 1000060806793 CreatorName Murata, Koichi
	CreatorName Jinno, Sadao
	NRID 1000010330078 1000010330078 CreatorName Takeuchi, Tohru
	NRID 1000010527708 1000010527708 Scopus Author ID 8883255100 8883255100 CreatorName Hirao, Makoto
	NRID 1000010294125 1000010294125 researchmap permalink read0051725 read0051725 Scopus Author ID 6602726311 6602726311 ORCID 0000-0003-4749-7117 0000-0003-4749-7117 CreatorName Kumanogoh, Atsushi
	NRID 1000060191558 1000060191558 CreatorName Yoshikawa, Hideki
Subject	ANSWER cohort
	Biological disease-modifying antirheumatic drugs
	Discontinuation
	Rheumatoid arthritis
Description	Ebina K., Hashimoto M., Yamamoto W., et al. Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis - The ANSWER cohort study. Arthritis Research and Therapy 21, 91 (2019); https://doi.org/10.1186/s13075-019-1880-4.
Abstract	Background: The aim of this study is to evaluate the retention rates and reasons for discontinuation for seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). Methods: This multi-center, retrospective study assessed 4466 treatment courses of 2494 patients with bDMARDs from 2009 to 2017 (females, 82.4%; baseline age, 57.4 years; disease duration 8.5 years; rheumatoid factor positivity 78.6%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.3; concomitant prednisolone (PSL) 2.7 mg/day (43.1%) and methotrexate (MTX) 5.0 mg/week (61.8%); and 63.6% patients were bio-naïve). Treatment courses included tocilizumab (TCZ; n = 895), etanercept (ETN; n = 891), infliximab (IFX; n = 748), abatacept (ABT; n = 681), adalimumab (ADA; n = 558), golimumab (GLM; n = 464), and certolizumab pegol (CZP; n = 229). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential confounders (age, sex, disease duration, concomitant PSL and MTX, and switched number of bDMARDs) using Cox proportional hazards modeling. Results: A total of 56.9% of treatment courses were stopped, with 25.8% stopping due to lack of effectiveness, 12.7% due to non-toxic reasons, 11.9% due to toxic adverse events, and 6.4% due to disease remission. Drug retention rates for each discontinuation reason were as follows: lack of effectiveness [from 65.5% (IFX) to 81.7% (TCZ); with significant differences between groups (Cox P < 0.001)], toxic adverse events [from 81.8% (IFX) to 94.0% (ABT), Cox P < 0.001], and remission [from 92.4% (ADA and IFX) to 97.7% (ETN), Cox P < 0.001]. Finally, overall retention rates excluding non-toxic reasons and remission for discontinuation ranged from 53.4% (IFX) to 75.5% (ABT) (Cox P < 0.001). Conclusions: TCZ showed the lowest discontinuation rate by lack of effectiveness, ABT showed the lowest discontinuation rate by toxic adverse events, ADA and IFX showed the highest discontinuation rate by remission, and ABT showed the highest overall retention rates (excluding non-toxic reasons and remission) among seven bDMARDs in the adjusted model.
Publisher	BioMed Central Ltd
Source Title	Arthritis Research and Therapy
Volume (Issue)	21(1)
Page	91
Date of Issued	2019-12-01
Language	English
Handle URL	https://hdl.handle.net/11094/93210
PISSN	14786354
eISSN	14786362
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1186/s13075-019-1880-4
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Arthritis Research and Therapy. 2019, 21(1), p. 91
DC.title	Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis - The ANSWER cohort study
DC.creator	Ebina, Kosuke
	Hashimoto, Motomu
	Yamamoto, Wataru
	Hirano, Toru
	Hara, Ryota
	Katayama, Masaki
	Onishi, Akira
	Nagai, Koji
	Son, Yonsu
	Amuro, Hideki
	Yamamoto, Keiichi
	Maeda, Yuichi
	Murata, Koichi
	Jinno, Sadao
	Takeuchi, Tohru
	Hirao, Makoto
	Kumanogoh, Atsushi
	Yoshikawa, Hideki
DC.publisher	BioMed Central Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2019-12-01
DC.identifier	https://doi.org/10.1186/s13075-019-1880-4
DC.subject	ANSWER cohort
	Biological disease-modifying antirheumatic drugs
	Discontinuation
	Rheumatoid arthritis
DC.description	Ebina K., Hashimoto M., Yamamoto W., et al. Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis - The ANSWER cohort study. Arthritis Research and Therapy 21, 91 (2019); https://doi.org/10.1186/s13075-019-1880-4.
DCTERMS.abstract	Background: The aim of this study is to evaluate the retention rates and reasons for discontinuation for seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). Methods: This multi-center, retrospective study assessed 4466 treatment courses of 2494 patients with bDMARDs from 2009 to 2017 (females, 82.4%; baseline age, 57.4 years; disease duration 8.5 years; rheumatoid factor positivity 78.6%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.3; concomitant prednisolone (PSL) 2.7 mg/day (43.1%) and methotrexate (MTX) 5.0 mg/week (61.8%); and 63.6% patients were bio-naïve). Treatment courses included tocilizumab (TCZ; n = 895), etanercept (ETN; n = 891), infliximab (IFX; n = 748), abatacept (ABT; n = 681), adalimumab (ADA; n = 558), golimumab (GLM; n = 464), and certolizumab pegol (CZP; n = 229). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential confounders (age, sex, disease duration, concomitant PSL and MTX, and switched number of bDMARDs) using Cox proportional hazards modeling. Results: A total of 56.9% of treatment courses were stopped, with 25.8% stopping due to lack of effectiveness, 12.7% due to non-toxic reasons, 11.9% due to toxic adverse events, and 6.4% due to disease remission. Drug retention rates for each discontinuation reason were as follows: lack of effectiveness [from 65.5% (IFX) to 81.7% (TCZ); with significant differences between groups (Cox P < 0.001)], toxic adverse events [from 81.8% (IFX) to 94.0% (ABT), Cox P < 0.001], and remission [from 92.4% (ADA and IFX) to 97.7% (ETN), Cox P < 0.001]. Finally, overall retention rates excluding non-toxic reasons and remission for discontinuation ranged from 53.4% (IFX) to 75.5% (ABT) (Cox P < 0.001). Conclusions: TCZ showed the lowest discontinuation rate by lack of effectiveness, ABT showed the lowest discontinuation rate by toxic adverse events, ADA and IFX showed the highest discontinuation rate by remission, and ABT showed the highest overall retention rates (excluding non-toxic reasons and remission) among seven bDMARDs in the adjusted model.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93210
citation_title	Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis - The ANSWER cohort study
citation_author	Ebina, Kosuke
	Hashimoto, Motomu
	Yamamoto, Wataru
	Hirano, Toru
	Hara, Ryota
	Katayama, Masaki
	Onishi, Akira
	Nagai, Koji
	Son, Yonsu
	Amuro, Hideki
	Yamamoto, Keiichi
	Maeda, Yuichi
	Murata, Koichi
	Jinno, Sadao
	Takeuchi, Tohru
	Hirao, Makoto
	Kumanogoh, Atsushi
	Yoshikawa, Hideki
citation_publisher	BioMed Central Ltd
citation_language	English
citation_date	2019-12-01
citation_journal_title	Arthritis Research and Therapy
citation_volume	21
citation_issue	1
citation_firstpage	91
citation_doi	https://doi.org/10.1186/s13075-019-1880-4
citation_public_url	https://hdl.handle.net/11094/93210

Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis - The ANSWER cohort study

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