Patients with rheumatoid arthritis had improved disease activity and functional disability measures over 10 years in a single-center Japanese cohort, coinciding with increased use of biologic and targeted synthetic disease-modifying antirheumatic drugs and decreased glucocorticoid use.
Researchers analyzed data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort from 2012 to 2021. The annual cross-sectional analysis included 5,070 survey observations from 1,156 patients with rheumatoid arthritis. A separate longitudinal analysis evaluated 1,816 new biologic or targeted synthetic disease-modifying antirheumatic drug prescriptions, including 820 among treatment-naïve patients and 996 among patients who switched therapies.
From 2012 to 2021, biologic or targeted synthetic disease-modifying antirheumatic drug use increased from 30% to 53%, while glucocorticoid use decreased from 41% to 19%. Methotrexate use remained above 60% throughout the study period, although it declined from 71% to 64%. The cohort also aged over time, with mean patient age increasing from 62.9 years to 65.9 years and patients younger than 60 years comprising less than 20% of the cohort by 2021.
Disease Activity Score 28-C-reactive protein remission increased to 80% in 2021, and Clinical Disease Activity Index remission increased from 25% to 48% over the study period. Median Health Assessment Questionnaire Disability Index scores decreased from 0.69 to 0.25.
In mixed-effects models adjusted for patient characteristics, treatment use, and disease severity measures, annual improvements remained statistically significant for Clinical Disease Activity Index and Health Assessment Questionnaire Disability Index, but not Disease Activity Score 28-C-reactive protein. The researchers suggested Disease Activity Score 28-C-reactive protein may have become less sensitive once approximately 80% of patients reached remission by that measure.
The researchers also assessed outcomes by treatment mechanism using propensity-score matching, with abatacept as the reference group because it served as a consistently prescribed comparator across the study period. Among biologic or targeted synthetic disease-modifying antirheumatic drug-naïve patients, tumor necrosis factor inhibitors showed greater improvement in Disease Activity Score 28-C-reactive protein and Clinical Disease Activity Index at 1 and 2 months compared with abatacept, but those differences were no longer statistically significant at later time points. Interleukin-6 receptor inhibitors showed greater improvement in some disease activity measures through 12 months compared with abatacept. Janus kinase inhibitors were excluded from the naïve-patient matched analysis because of small numbers, although their use increased during the study period and exceeded 20% of naïve-patient initiations in later years.
Among patients who switched therapies, disease activity and functional disability measures were generally comparable across treatment mechanisms in the propensity-matched comparisons. However, interleukin-6 receptor inhibitors had higher drug retention in switched patients despite the absence of statistically superior disease activity or functional disability outcomes in the matched analyses. In the retention analysis, discontinuation because of inefficacy or adverse events was counted as an event, whereas discontinuation because of remission, socioeconomic issues, or patient preference was censored.
Concomitant methotrexate use also varied by treatment mechanism. Among treatment-naïve patients and switched patients, respectively, methotrexate was used with tumor necrosis factor inhibitors in 75% and 63% of cases, with interleukin-6 receptor inhibitors in 41% and 57%, with abatacept in 47% and 49%, and with Janus kinase inhibitors in 62% and 47%.
The researchers cautioned that treatment selection may have been influenced by unmeasured factors, including comorbidities, allergy history, socioeconomic status, and other confounders. The annual survey also did not include all patients with rheumatoid arthritis treated at the hospital. The single-center Japanese cohort, local prescribing patterns, treatment approval timelines, and aging patient population may limit generalizability to other practice settings.
“In summary, we reviewed the real-world transition of therapeutic strategies and their outcomes in the 10-year history of the KURAMA cohort,” wrote lead study author Takayuki Fujii, of Kyoto University Graduate School of Medicine, and colleagues. “The disease activity and functional disability metrics of patients with RA improved over a decade with increased use of b/tsDMARDs.”
Disclosures: The KURAMA cohort study was supported by Daiichi Sankyo Co Ltd. The Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine, was supported by Nagahama City, Toyooka City, Asahi Kasei Pharma Corp, and AYUMI Pharmaceutical Co. Multiple researchers reported speaker fees, consulting fees, honoraria, or research funding from pharmaceutical companies. The funders were not involved in the study design, data collection, analysis, interpretation, manuscript writing, or publication decision.
Source: Arthritis Research & Therapy
