Real-world clinical outcomes of patients with disproportionate articular pain in rheumatoid arthritis: ANSWER cohort study

PURPOSE: In rheumatoid arthritis (RA), some patients experience joint pain that is disproportionate to the number of swollen joints, known as disproportionate articular pain (DP). This study aimed to clarify the prevalence and persistence of DP and to compare the outcomes across biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). MATERIALS AND METHODS: From the ANSWER cohort in Japan, 5489 RA patients who initiated b/tsDMARDs between January 2010 and June 2024 were screened. DP was defined as having at least seven more tender joints (TJC) than swollen joints at baseline, and 432 patients met this criterion. Persistence of DP at 3 and 6 months was evaluated. Comparative analyses were conducted across mechanisms of action (MOAs): tumour necrosis factor-α inhibitors (TNFi), cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (CTLA4-Ig), interleukin-6 inhibitors (IL-6i), and Janus kinase inhibitors (JAKi). RESULTS: DP was identified in 7.8% of RA patients. At 3 months, DP persisted in 40.7% (TNFi), 36.5% (CTLA4-Ig), 48.0% (IL-6i), and 54.4% (JAKi). At 6 months, corresponding rates were 43.8%, 38.7%, 49.3%, and 61.1%. Multivariate analysis showed that higher TJC and previous treatment with two or more b/tsDMARDs were associated with persistent DP, whereas higher C-reactive protein was protective. Within JAKi, baricitinib showed lower DP persistence compared with other JAKi. CONCLUSION: DP was present in approximately 8% of RA patients. Persistent DP was associated with higher TJC, greater number of previous b/tsDMARDs, and lower inflammation. No MOA was clearly superior; however, baricitinib may confer a relative benefit within the JAKi class.