Clinical and healthcare burden of difficult-to-treat rheumatoid arthritis in Japan: a retrospective cohort study
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Objectives To quantify the clinical burden and healthcare resource use (HCRU) associated with difficult-to-treat (D2T) rheumatoid arthritis (RA) compared with non-D2T RA and evaluate clinical characteristics and factors associated with D2T RA as well as treatment patterns in Japan.
Design Longitudinal, retrospective observational study using electronic medical record data from 1992 to 2024 and a physician survey administered between November 2022 and November 2025.
Setting A single academic medical centre real-world clinical practice setting in Japan.
Participants A total of 1581 patients with RA were included.
Primary and secondary outcome measures The primary outcome measures were the comparisons of clinical burden and HCRU in the D2T RA group compared with the non-D2T RA group. D2T RA status was defined according to the European Alliance of Associations for Rheumatology definition. Clinical burden included disease activity, physical function, patient-reported outcomes, serological markers and renal function. HCRU included outpatient visits and hospitalisations evaluated over 12-month, 24-month and 36 month windows pre-index using overlap weighting and regression models. Factors associated with D2T RA status were evaluated using logistic regression. Treatment patterns were reconstructed longitudinally as lines of therapy across biologic and targeted synthetic disease-modifying antirheumatic drugs.
Results Among 1581 patients with RA, 102 (6.5%) met the D2T criteria. Treatment trajectories showed earlier escalation and frequent switching across biologic and targeted synthetic disease-modifying antirheumatic drugs in the D2T RA group. The D2T RA group had modestly elevated outpatient visit rates (rate ratio 1.08–1.09) and were more likely to be hospitalised (OR 4.35–6.12) than the non-D2T RA group. Factors associated with D2T RA included RA onset at age <50 (adjusted OR versus ≥50 years: 2.01, 95% CI 1.19 to 3.39), female sex (2.38, 95% CI 0.95 to 5.94) and pulmonary comorbidities (2.82, 95% CI 1.38 to 5.74).
Conclusions In this real-world Japanese cohort, D2T RA was associated with higher disease burden and HCRU, particularly hospital-based care. Earlier identification and targeted management of D2T RA may help reduce the overall clinical and healthcare burden in RA.
Design Longitudinal, retrospective observational study using electronic medical record data from 1992 to 2024 and a physician survey administered between November 2022 and November 2025.
Setting A single academic medical centre real-world clinical practice setting in Japan.
Participants A total of 1581 patients with RA were included.
Primary and secondary outcome measures The primary outcome measures were the comparisons of clinical burden and HCRU in the D2T RA group compared with the non-D2T RA group. D2T RA status was defined according to the European Alliance of Associations for Rheumatology definition. Clinical burden included disease activity, physical function, patient-reported outcomes, serological markers and renal function. HCRU included outpatient visits and hospitalisations evaluated over 12-month, 24-month and 36 month windows pre-index using overlap weighting and regression models. Factors associated with D2T RA status were evaluated using logistic regression. Treatment patterns were reconstructed longitudinally as lines of therapy across biologic and targeted synthetic disease-modifying antirheumatic drugs.
Results Among 1581 patients with RA, 102 (6.5%) met the D2T criteria. Treatment trajectories showed earlier escalation and frequent switching across biologic and targeted synthetic disease-modifying antirheumatic drugs in the D2T RA group. The D2T RA group had modestly elevated outpatient visit rates (rate ratio 1.08–1.09) and were more likely to be hospitalised (OR 4.35–6.12) than the non-D2T RA group. Factors associated with D2T RA included RA onset at age <50 (adjusted OR versus ≥50 years: 2.01, 95% CI 1.19 to 3.39), female sex (2.38, 95% CI 0.95 to 5.94) and pulmonary comorbidities (2.82, 95% CI 1.38 to 5.74).
Conclusions In this real-world Japanese cohort, D2T RA was associated with higher disease burden and HCRU, particularly hospital-based care. Earlier identification and targeted management of D2T RA may help reduce the overall clinical and healthcare burden in RA.
Date Acceptance
2026-08-13
Citation
BMJ Open, 16 (8)
ISSN
2044-6055
Publisher
BMJ Publishing Group
Journal / Book Title
BMJ Open
Volume
16
Issue
8
Copyright Statement
© The Author(s). This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non- commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non- commercial. See: https://creativecommons.org/licenses/by-nc/4.0/.
License URL
Identifier
10.1136/bmjopen-2026-120136
Publication Status
Published
Article Number
120136
Date Publish Online
2026-08-26