Complex Evolution of RA Management and Outcomes Save

FIRST is a Japanese longitudinal, real-world registry of rheumatoid arthritis (RA) management, and over the last 20 years has shown significantly improved outcomes, yet significant challenges and unmet needs remain.

FIRST registry is a multicenter cohort of patients with RA treated with biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Between 2003 and 2023, patients were followed for 60 months and assessed for drug efficacy, retention, and reasons for discontinuation.

Analysis of 5130 treatments over 16,616 person-years revealed significant shifts in demographics and outcomes:

• Age at initiation or switch to b/tsDMARDs increased (51.9–64.3 years) 
• Increasing comorbidities 
  • lung disease: 11.1–36.2%
  • malignancy: 2.2–13.1%
  • fragility fractures 4.4–20.8%
  • major adverse cardiovascular events (MACE): 2.2–9.4%) 
  • thrombosis 2.2–4.0%
• b/tsDMARD use expanded to use in  patients with lower disease activity. 
• Improved disease control
• Higher remission rates in DMARD naïve group but unchanged in those on prior b/tsDMARDs group 
• Methotrexate use has decreased from 100% to 67.2% by 2023 
  • (while average dose increased from 6.8 to 11.4 mg/week). 
• Concomitant glucocorticoid use decreased markedly from 66.7 to 21.1%
• Adverse event drug discontinuations decreased (eg, infections fell from 2.1 to 0.7 per 100 PYs)
• Retention rates varied - lowest with TNF inhibitors, higer with IL-6 receptor inhibitors abatacept
  • TNFi had high remission rates but low retention
  • CTLA4-Ig and IL-6Ri had lower remission rates and higher retention
• Changes in functional improvement were modest, but in the elderly (aged 75 years and older), functional gains remained limited.

The study highlights the evolving landscape of RA management in an aging society. While many RA outcomes are better, RA has become more complex to manage. Unmet needs still persist for those not achieving treat-to-target goals and those with limited functional improvement.