Patients and study design
We conducted a retrospective cohort study at the Department of Rheumatology, Fukushima Medical University Hospital and Fukushima Red Cross hospital. Among 601 elderly patients (age ≥65 years; Female 413, Male 189) diagnosed with RA during the study period (between July 1, 2016 and December 2021), 134 consecutive elderly (age ≥65 years) patients who were initiated with bDMARDs or tsDMARDs were enrolled. All the patients met the 1987 American College of Rheumatology (ACR) classification criteria for RA  and could be longitudinally followed up until 52 weeks after initiation of bDMARDs or tsDMARDs. The following bDMARDS were used in our cohort: 18 tumor necrosis factor inhibitors (TNFi) (9 etanercept, 8 golimumab, and 1 certolizumab pegol), 30 interleukin-6 inhibitors (IL-6i) (29 tocilizumab or 1 sarilumab), and 32 abatacept. The tsDMARDS included 54 JAKi (14 tofacitinib, 36 baricitinib, and 4 upadacitinib). This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval for this study (No.2020-110) was provided by the Ethics Committee of Fukushima Medical University.
At the start of treatment, baseline data were collected from medical records, including demographics (age, gender), disease characteristics (disease duration, titers of anticyclic citrullinated protein [CCP] antibody and rheumatoid factor [RF]), measures of disease activity (swollen joint count [SJC], tender joint count [TJC], patient global assessment [PtGA], physician global assessment [PGA]), and C-reactive protein [CRP], and treatment details (current glucocorticoid and MTX doses, previous use of csDMARDs and b/tsDMARDs). Treatment selection was at the discretion of the treating physician, based on the clinical condition, presence of geographical barriers to transportation, and possibility of greater adherence. Disease activity score in 28 joints using CRP (DAS28-CRP) were also retrieved from the records.
Serial assessments of disease activity including laboratory parameters and treatment-related information regarding disease activity were collected at every 4 weeks after initiation of therapy. If treatment was discontinued, the date and reason of discontinuation were recorded. Clinical response after 24 weeks after the start of treatment was assessed according to the European Alliance of Associations for Rheumatology (EULAR) response as follows : Good responders: improvement > 1.2, and a present DAS28 ≤ 3.2. Moderate responders: improvement > 0.6 to ≤1.2, and a present DAS28 ≤ 5.1; or improvement > 1.2, and a present DAS28 > 3.2. Nonresponders: improvement ≤ 0.6, or improvement > 0.6 to ≤1.2, and a present DAS28 > 5.1. Type and number of adverse events that had caused bDMARDs of tsDMARDs discontinuation were examined. Decisions to discontinue these DMARDs due to adverse events were made by the treating physicians based on a comprehensive evaluation of physical findings, laboratory findings and radiological examinations.
Continuous variables were presented as mean ± standard deviation or median (interquartile range) and categorical variables were presented as frequency (percentage). The chi-squared test was used to compare categorical variables, and the Mann-Whitney U test was used to compare continuous variables. Drug retention was analyzed using Kaplan–Meier plots and between-group differences assessed using the log-rank test. Cumulative incidences of discontinuation due to lack of effectiveness or adverse effects were compared using the Log-rank test for the Kaplan-Meier model. Data processing and statistical analyses were performed using SPSS Statistics (version 25.0 for Windows, Chicago, IL, USA). Two–tailed p values <0.05 were considered indicative of statistical significance.