Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the ANSWER cohort study
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 assesse...
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BMC
2019-04-01
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Series: | Arthritis Research & Therapy |
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Online Access: | http://link.springer.com/article/10.1186/s13075-019-1880-4 |
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doaj-8276c108654a42928fa6b40574c6e116 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kosuke Ebina Motomu Hashimoto Wataru Yamamoto Toru Hirano Ryota Hara Masaki Katayama Akira Onishi Koji Nagai Yonsu Son Hideki Amuro Keiichi Yamamoto Yuichi Maeda Koichi Murata Sadao Jinno Tohru Takeuchi Makoto Hirao Atsushi Kumanogoh Hideki Yoshikawa |
spellingShingle |
Kosuke Ebina Motomu Hashimoto Wataru Yamamoto Toru Hirano Ryota Hara Masaki Katayama Akira Onishi Koji Nagai Yonsu Son Hideki Amuro Keiichi Yamamoto Yuichi Maeda Koichi Murata Sadao Jinno Tohru Takeuchi Makoto Hirao Atsushi Kumanogoh Hideki Yoshikawa Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the ANSWER cohort study Arthritis Research & Therapy ANSWER cohort Biological disease-modifying antirheumatic drugs Discontinuation Rheumatoid arthritis |
author_facet |
Kosuke Ebina Motomu Hashimoto Wataru Yamamoto Toru Hirano Ryota Hara Masaki Katayama Akira Onishi Koji Nagai Yonsu Son Hideki Amuro Keiichi Yamamoto Yuichi Maeda Koichi Murata Sadao Jinno Tohru Takeuchi Makoto Hirao Atsushi Kumanogoh Hideki Yoshikawa |
author_sort |
Kosuke Ebina |
title |
Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the ANSWER cohort study |
title_short |
Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the ANSWER cohort study |
title_full |
Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the ANSWER cohort study |
title_fullStr |
Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the ANSWER cohort study |
title_full_unstemmed |
Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the ANSWER cohort study |
title_sort |
drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the answer cohort study |
publisher |
BMC |
series |
Arthritis Research & Therapy |
issn |
1478-6362 |
publishDate |
2019-04-01 |
description |
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. |
topic |
ANSWER cohort Biological disease-modifying antirheumatic drugs Discontinuation Rheumatoid arthritis |
url |
http://link.springer.com/article/10.1186/s13075-019-1880-4 |
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doaj-8276c108654a42928fa6b40574c6e1162020-11-25T02:06:28ZengBMCArthritis Research & Therapy1478-63622019-04-0121111010.1186/s13075-019-1880-4Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the ANSWER cohort studyKosuke Ebina0Motomu Hashimoto1Wataru Yamamoto2Toru Hirano3Ryota Hara4Masaki Katayama5Akira Onishi6Koji Nagai7Yonsu Son8Hideki Amuro9Keiichi Yamamoto10Yuichi Maeda11Koichi Murata12Sadao Jinno13Tohru Takeuchi14Makoto Hirao15Atsushi Kumanogoh16Hideki Yoshikawa17Department of Orthopaedic Surgery, Osaka University, Graduate School of MedicineDepartment of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto UniversityDepartment of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto UniversityDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of MedicineThe Center for Rheumatic Diseases, Nara Medical UniversityDepartment of Rheumatology, Osaka Red Cross HospitalDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of MedicineDepartment of Internal Medicine (IV), Osaka Medical CollegeFirst Department of Internal Medicine, Kansai Medical UniversityFirst Department of Internal Medicine, Kansai Medical UniversityDepartment of Medical Informatics, Wakayama Medical University HospitalDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of MedicineDepartment of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto UniversityDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of MedicineDepartment of Internal Medicine (IV), Osaka Medical CollegeDepartment of Orthopaedic Surgery, Osaka University, Graduate School of MedicineDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of MedicineDepartment of Orthopaedic Surgery, Osaka University, Graduate School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s13075-019-1880-4ANSWER cohortBiological disease-modifying antirheumatic drugsDiscontinuationRheumatoid arthritis |