Targeted Therapies for Rheumatoid Arthritis in Super-Elderly Society: Insights From FIRST Registry, Japan

Abstract

As the world's most rapidly aging society, Japan has faced significant challenges in the management of rheumatoid arthritis (RA) in elderly patients. Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) have improved disease control, but concerns remain regarding the risk of infection and malignancy, especially in the elderly population. This review presents real-world data from FIRST registry, a prospective cohort following a total of 5500 patients over 20 years, and highlights strategies to balance efficacy and safety. Registry shows an increasing age of patients initiating b/tsDMARDs and an increase in comorbidities such as cardiovascular disease, chronic kidney disease, and malignancies. Infection control—including prophylaxis against pneumocystis pneumonia, screening for non-tuberculous mycobacteria, and vaccination—has been associated with a lower incidence of serious infections. Similarly, a proactive malignancy management strategy that includes computed tomography (CT) screening and multidisciplinary care has been correlated with improved detection of early-stage cancers and fewer treatment discontinuations due to malignancy. While these findings represent associations rather than direct causal effects, they reflect the evolving landscape of RA management over two decades. Meanwhile, the registry highlights unmet needs, particularly in patients with prior b/tsDMARD exposure, who often experience lower response rates. In addition, while clinical remission rates have improved, functional outcomes remain suboptimal, particularly in older patients. To address these challenges, personalized treatment selection is being explored. By sharing Japan's experience in managing RA in an aging society, this review provides insights into strategies that may be applicable to other aging populations worldwide.