Abstract

This multi-center, retrospective study aimed to clarify the factors affecting drug retention of the Janus kinase inhibitors (JAKi) including baricitinib (BAR) and tofacitinib (TOF) in patients with RA. Patients were as follows; females, 80.6%; age, 60.5 years; DAS28-ESR, 4.3; treated with either BAR (n = 166) or TOF (n = 185); bDMARDs- or JAKi-switched cases (76.6%). The reasons for drug discontinuation were classified into four major categories. The drug retention was evaluated at 24 months using the Kaplan–Meier method and multivariate Cox proportional hazards modelling adjusted by confounders. Discontinuation rates for the corresponding reasons were as follows; ineffectiveness (22.3%), toxic adverse events (13.3%), non-toxic reasons (7.2%) and remission (0.0%). Prior history of anti-interleukin-6 receptor antibody (aIL-6R) ineffectiveness significantly increased the risk of treatment discontinuation due to ineffectiveness (p = 0.020). Aging (≥ 75 years) (p = 0.028), usage of PSL ≥ 5 mg/day (p = 0.017) and female sex (p = 0.041) significantly increased the risk of treatment discontinuation due to toxic adverse events. Factors not associated with treatment discontinuation were: number of prior bDMARDs or JAKi, concomitant MTX usage, difference of JAKi, and prior use of TNF inhibitor, CTLA4-Ig or other JAKi.

Details

Title
Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study
Author
Ebina Kosuke 1   VIAFID ORCID Logo  ; Hirano Toru 2 ; Maeda Yuichi 3 ; Yamamoto Wataru 4 ; Hashimoto Motomu 5 ; Murata Koichi 6 ; Onishi Akira 6 ; Jinno Sadao 7 ; Hara Ryota 8 ; Son Yonsu 9 ; Amuro Hideki 9 ; Takeuchi Tohru 10 ; Yoshikawa Ayaka 10 ; Katayama Masaki 11 ; Yamamoto Keiichi 12 ; Okita Yasutaka 13 ; Hirao Makoto 14 ; Etani Yuki 14 ; Kumanogoh Atsushi 3 ; Okada Seiji 14 ; Nakata, Ken 15 

1  Osaka University Graduate School of Medicine, Department of Musculoskeletal Regenerative Medicine, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
2  Nishinomiya Municipal Hospital, Department of Rheumatology, Hyogo, Japan (GRID:grid.136593.b) 
3  Osaka University Graduate School of Medicine, Department of Respiratory Medicine and Clinical Immunology, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971); Osaka University, Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
4  Kurashiki Sweet Hospital, Department of Health Information Management, Okayama, Japan (GRID:grid.136593.b); Kyoto University, Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
5  Kyoto University, Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); Osaka City University Graduate School of Medicine, Department of Clinical Immunology, Osaka, Japan (GRID:grid.261445.0) (ISNI:0000 0001 1009 6411) 
6  Kyoto University, Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
7  Kobe University Graduate School of Medicine, Department of Rheumatology and Clinical Immunology, Hyogo, Japan (GRID:grid.31432.37) (ISNI:0000 0001 1092 3077) 
8  Nara Medical University, Department of Orthopaedic Surgery, Nara, Japan (GRID:grid.410814.8) (ISNI:0000 0004 0372 782X) 
9  Kansai Medical University, First Department of Internal Medicine, Osaka, Japan (GRID:grid.410783.9) (ISNI:0000 0001 2172 5041) 
10  Osaka Medical and Pharmaceutical University, Department of Internal Medicine (IV), Osaka, Japan (GRID:grid.410783.9) 
11  Osaka Red Cross Hospital, Department of Rheumatology, Osaka, Japan (GRID:grid.417000.2) (ISNI:0000 0004 1764 7409) 
12  Wakayama Medical University, Information Technology Center, Wakayama, Japan (GRID:grid.412857.d) (ISNI:0000 0004 1763 1087) 
13  Osaka University Graduate School of Medicine, Department of Respiratory Medicine and Clinical Immunology, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
14  Osaka University Graduate School of Medicine, Department of Orthopaedic Surgery, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
15  Osaka University Graduate School of Medicine, Department of Health and Sport Sciences, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-021-04075-0
ProQuest document ID
2619581976
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.