Japanese evidence on Janus kinase inhibitors for rheumatoid arthritis: a narrative review of risk-optimized use

Background Janus kinase inhibitors (JAKi) have expanded treatment options for rheumatoid arthritis (RA) by providing rapid and effective oral therapy. However, their optimal use has become increasingly complex after the emergence of safety concerns involving serious infections, herpes zoster (HZ), major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancy. This issue is particularly relevant in Japan, where the RA population is older and has a higher prevalence of comorbidities. Objective To review the risk-optimized use of JAKi for RA based on Japanese evidence, with particular emphasis on older patients, comorbidity-rich populations, and practical real-world treatment decision-making. Evidence acquisition We conducted a literature search of PubMed/MEDLINE and Ichushi-Web to identify Japan-specific studies on JAKi in RA. Randomized trials, long-term extension studies, registry analyses, database studies, postmarketing surveillance reports, and observational studies were reviewed. Because of heterogeneity in design, patient background, and outcome definitions, the evidence was synthesized narratively. Content Japanese evidence indicates that older age is an important but insufficient determinant of JAKi safety. Across studies, treatment outcomes were more strongly influenced by comorbidities, glucocorticoid exposure, laboratory abnormalities, and other patient-related risk factors. HZ emerged as the most consistent safety signal, supporting the importance of vaccination and early monitoring. By contrast, the risk of hospitalized infection was not consistently higher with JAKi than with biologic disease-modifying antirheumatic drugs in older patients, and Japanese evidence on MACE, VTE, and malignancy remained limited or inconsistent. Real-world studies also supported individualized dose optimization, whereas current data did not support routine within-class selection based primarily on JAK selectivity. Conclusion Current Japanese evidence supports a risk-optimized approach to the use of JAKi in RA. Age alone should not determine treatment decisions. Instead, rheumatologists should individualize JAKi selection, dosing, and monitoring according to comorbidity profile, infection and vascular risk, malignancy background, and therapeutic priorities, particularly in increasingly older and multimorbid patients.