# Five-Year Drug Survival and Discontinuation Reasons for Eight Biological Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis: A Retrospective Analysis of 1182 Patients from the Niigata Orthopedic Surgery Rheumatoid Arthritis Database (NOSRAD)

## TL;DR

This study analyzed 5-year drug survival and discontinuation reasons for eight biologic drugs used to treat rheumatoid arthritis in over 1,000 patients.

## Contribution

The study provides real-world 5-year drug survival data and identifies factors influencing discontinuation for various biologic treatments in rheumatoid arthritis.

## Key findings

- Tocilizumab had the highest 5-year drug survival (50.8%) in biologic-naïve patients, while golimumab had the lowest (22.6%).
- Male sex, lower baseline DAS28-ESR, and absence of methotrexate co-therapy predicted discontinuation in biologic-naïve patients.
- Inadequate response was the most common reason for discontinuation (27.1%), followed by non-adverse events (25.3%).

## Abstract

Background: Continuity of care for rheumatoid arthritis patients within regional networks enables stable long-term clinical data collection, despite chronic rheumatologist shortages in Japan. We determined 5-year drug survival and discontinuation reasons for eight biological disease-modifying antirheumatic drugs (bDMARDs) using a regional multicenter registry. Methods: We retrospectively analyzed 1182 patients initiating their first (naïve, n = 784) or subsequent (switch, n = 398) bDMARD between May 2001 and August 2022 across five institutions. The primary endpoint (5-year drug survival) and secondary endpoints (discontinuation risk factors and cumulative incidence of reasons) were evaluated using Kaplan–Meier curves, Cox proportional hazards, and Fine & Gray models. Results: Baseline characteristics varied significantly among bDMARDs. Five-year drug survival in the naïve cohort ranged from tocilizumab (50.8%) to golimumab (22.6%); in the switch cohort, from abatacept (42.6%) to infliximab (10.0%). In multivariable Cox analysis of naïve patients, male sex (hazard ratio [HR] = 1.49, 95% confidence interval [CI] = 1.09–2.02), lower baseline 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) (HR = 0.90, 95% CI = 0.82–0.99), and absence of methotrexate co-therapy (HR = 0.73, 95% CI = 0.55–0.97) predicted discontinuation. The lower baseline DAS28-ESR association potentially reflects successful courses toward intentional cessation following remission. Discontinuations were attributed to inadequate response (27.1%), non-adverse events (25.3%), and adverse events (17.3%). Conclusions: Tocilizumab and abatacept demonstrated the highest retention rates in biologic-naïve and switch cohorts, respectively. Early, individualized drug selection and dose optimization are crucial to maximizing long-term bDMARD effectiveness before switching.