Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis -The ANSWER cohort study

• Published in: PloS one 2018-03, Vol.13 (3), p.e0194130
• Main Authors: Ebina, Kosuke, Hashimoto, Motomu, Yamamoto, Wataru, Ohnishi, Akira, Kabata, Daijiro, Hirano, Toru, Hara, Ryota, Katayama, Masaki, Yoshida, Shuzo, Nagai, Koji, Son, Yonsu, Amuro, Hideki, Akashi, Kengo, Fujimura, Takanori, Hirao, Makoto, Yamamoto, Keiichi, Shintani, Ayumi, Kumanogoh, Atsushi, Yoshikawa, Hideki
• Format: Article
• Language: English
• Subjects: Analysis; Antirheumatic agents; Arthritis; Biology and Life Sciences; Clinical medicine; Cohort analysis; Complications and side effects; Dosage and administration; Drug therapy; Erythrocyte sedimentation rate; Erythrocytes; Etanercept; Hazards; Hospitals; Immunology; Infliximab; Internal medicine; Joint diseases; Medical statistics; Medicine; Medicine and Health Sciences; Methotrexate; Modelling; Monoclonal antibodies; Patients; Physical Sciences; Prednisolone; Product discontinuation; Remission; Research and Analysis Methods; Retention; Rheumatic diseases; Rheumatoid arthritis; Rheumatoid factor; Rheumatology; Studies; Surgery; Tumor necrosis factor-α; University graduates
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0194130

The purpose of this study was to evaluate the retention and discontinuation reasons of seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). 1,037 treatment courses with bDMARDs from 2009 to 2016 [female, 81.8%; baseline age, 59.6 y; disease duration 7.8 y; rheumatoid factor positivity 81.5%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), 4.4; concomitant prednisolone 43.5% and methotrexate 68.6%; Bio-naïve, 57.1%; abatacept (ABT), 21.3%; tocilizumab (TCZ), 20.7%; golimumab (GLM), 16.9%; etanercept (ETN), 13.6%; adalimumab (ADA), 11.1%; infliximab (IFX), 8.5%; certolizumab pegol (CZP), 7.9%] were included in this multi-center, retrospective study. Drug retention and discontinuation reasons at 36 months were estimated using the Kaplan-Meier method and adjusted by potent confounders using Cox proportional hazards modeling. As a result, 455 treatment courses (43.9%) were stopped, with 217 (20.9%) stopping due to inefficacy, 113 (10.9%) due to non-toxic reasons, 86 (8.3%) due to toxic adverse events, and 39 (3.8%) due to remission. Drug retention rates in the adjusted model were as follows: total retention (ABT, 60.7%; ADA, 32.7%; CZP, 43.3%; ETN, 51.9%; GLM, 45.4%; IFX, 31.1%; and TCZ, 59.2%; P < 0.001); inefficacy (ABT, 81.4%; ADA, 65.7%; CZP, 60.7%; ETN, 71.3%; GLM, 68.5%; IFX, 65.0%; and TCZ, 81.4%; P = 0.015), toxic adverse events (ABT, 89.8%; ADA, 80.5%; CZP, 83.9%; ETN, 89.2%; GLM, 85.5%; IFX, 75.6%; and TCZ, 77.2%; P = 0.50), and remission (ABT, 95.5%; ADA, 88.1%; CZP, 91.1%; ETN, 97.5%; GLM, 94.7%; IFX, 86.4%; and TCZ, 98.4%; P < 0.001). In the treatment of RA, ABT and TCZ showed higher overall retention, and TCZ showed lower inefficacy compared to IFX, while IFX showed higher discontinuation due to remission compared to ABT, ETN, GLM, and TCZ in adjusted modeling.