Effective Second-Line b/tsDMARDs for Patients with Rheumatoid Arthritis Unresponsive to First-Line b/tsDMARDs from...

For patients with rheumatoid arthritis (RA) unresponsive to first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), the selection of second-line b/tsDMARDs is crucial to prevent progression to difficult-to-treat rheumatoid arthritis (D2TRA). However, indicators for selection are lacking. This study aimed to identify optimal second-line b/tsDMARDs among the phase III treatment strategies based on European League Against Rheumatism (EULAR) RA management recommendations.

A total of 687 RA patients treated with second-line b/tsDMARDs (tumor necrosis factor inhibitor (n = 246), interleukin-6 receptor inhibitor [n = 195], cytotoxic T-lymphocyte-associated protein 4 immunoglobulin [n = 119], and Janus kinase inhibitor [n = 127]) were enrolled between October 2013 and April 2023. Rates of patients achieving Clinical Disease Activity Index (CDAI) remission and CDAI low disease activity (LDA), changes in CDAI, persistence rates, and adverse events within 24 weeks after treatment initiation were compared among the four groups. Propensity score-based inverse probability of treatment weighting (PS-IPTW) was used to minimize selection bias.

After PS-IPTW adjustment, the Janus kinase inhibitor (JAKi) group had the highest persistence rate among the four groups. At 24 weeks, the JAKi group showed the greatest improvement in CDAI and the highest CDAI remission rate. Among patients treated with JAKi as second-line b/tsDMARDs, upadacitinib (UPA) was most likely to achieve CDAI remission at 24 weeks. The comparison between the UPA group (n = 32) and the non-UPA JAKi group (tofacitinib and baricitinib [n = 95]) showed comparable persistence rates but significantly lower CDAI scores and higher CDAI remission rate at 24 weeks in the UPA group. No significant difference was noted in the overall incidence of adverse events among the four groups treated with b/tsDMARDs or between the groups treated with JAKi.

Selecting JAKi, especially UPA, may effectively improve the disease activity for RA patients unresponsive to first-line b/tsDMARDs. Further large-scale studies are needed to clarify the efficacy and safety of UPA.

FIRST registry (approval number#04-23): October 2013, retrospectively registered.