Real-world effectiveness of b/tsDMARD switching in low-inflammatory difficult-to-treat rheumatoid arthritis: insights from the FIRST registry

OBJECTIVES: To assess the effectiveness of switching biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients with low-inflammatory difficult-to-treat rheumatoid arthritis (D2T RA). METHODS: Using the multicentre FIRST registry, we identified D2T RA between August 2013 and March 2024. Low-inflammatory D2T RA was defined as a swollen 28-joint count ≤1 and C-reactive protein <10 mg/L. In the low-inflammatory D2T RA group, we compared those who underwent b/tsDMARD switching (the switch group) with the non-switch group. The primary outcome was the 6-month change in Clinical Disease Activity Index (CDAI). RESULTS: Among 3519 patients, 457 fulfilled the D2T RA criteria, and 173 were low-inflammatory D2T RA. Compared with inflammatory D2T RA, these patients had a shorter disease duration (127.4 vs 146.4 months), lower methotrexate (9.2 vs 10.5 mg/week) and glucocorticoid doses (4.3 vs 5.2 mg/day), and higher rates of fibromyalgia (2.9% vs 1.4%) and psychological disorders (5.2% vs 1.8%). The proportion receiving b/tsDMARD switching was lower in low-inflammatory than in inflammatory D2T RA (29/173 (16.8%) vs 217/284 (76.4%)). In the propensity score-matched analysis, the switch group (n=15) showed greater improvements in CDAI and pain than the non-switch group (n=30) (-6.6 vs -2.2, -15.3 vs -3.4, both p<0.05). Even among patients with low-grade sonographic activity (greyscale ≤1, power Doppler=0), b/tsDMARD switching improved CDAI (16.8 to 9.7). CONCLUSIONS: A subset of patients with low-inflammatory D2T RA may benefit from b/tsDMARD switching, indicating that low-inflammatory status alone should not preclude consideration of treatment intensification.