Real-World Safety and Efficacy of Targeted Therapies in Rheumatoid Arthritis: A 5-Year, 5130-Case Follow-Up from FIRST Registry
Koshiro Sonomoto, Shingo Nakayamada, Hiroaki Tanaka, Atsushi Nagayasu, Yoshiya Tanaka
Abstract
INTRODUCTION: This work aims to illustrate the evolution and ongoing challenges of rheumatoid arthritis (RA) management with targeted therapy over 20 years, using a cohort study from the world's oldest society. METHODS: Data were obtained from FIRST registry, a multicenter cohort of patients with RA treated with biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Patients were followed for 60 months and assessed for drug efficacy, retention, and reasons for discontinuation. RESULTS: Analysis of 5130 treatments over 16,616 person-years revealed shifts in strategies and demographics. Despite an aging population (51.9-64.3 years) with increasing comorbidities (lung disease: 11.1-36.2%, malignancy: 2.2-13.1%), b/tsDMARD use expanded to include patients with lower disease activity. With better disease control, discontinuations due to adverse events decreased, and particularly infections fell from 2.1 to 0.7 per 100 person-years. Remission rates improved over time in the naïve group but remained largely unchanged in the prior b/tsDMARDs group. Retention rates varied by bDMARD class, with TNF inhibitors (TNFi) showing a decrease over time and IL-6 receptor inhibitors (IL-6Ri) and CTLA4-Ig showing an increase in retention. TNFi had high remission rates but low retention, whereas CTLA4-Ig and IL-6Ri had lower remission rates and higher retention. Changes in functional improvement were modest overall, and in patients aged 75 years and older, functional gains remained limited. CONCLUSIONS: The study highlights the evolving landscape of RA management in an aging society, noting gains in efficacy and safety. However, unmet needs persist, particularly for patients not fully achieving treat-to-target goals and those with limited functional improvement.