Cytokine/chemokine profiles in rheumatoid arthritis patients who failed Boolean remission solely due to elevated patient global assessment.

Abstract

Rheumatoid arthritis (RA) patients achieving original Boolean remission require a tender joint count ≤1, swollen joint count ≤1, C-reactive protein ≤1 mg/dl, and a patient global assessment (PGA) ≤1. Approximately 30% of patients meet the objective criteria but fail remission solely due to elevated PGA, termed 'near-remission'. The underlying mechanisms remain unclear, with debate whether persistent symptoms reflect residual inflammation or non-inflammatory factors. This prospective cohort study analysed 200 RA patients receiving biologic/targeted synthetic disease-modifying antirheumatic drugs. Patients were stratified according to 12-month Boolean remission status as follows: complete remission (Group 0, n = 68), near-remission with elevated PGA only (Group 1, n = 50), and non-remission (Group 2, n = 82). We measured 41 cytokines/chemokines and auto-antibodies to characterize inflammatory profiles. At baseline, Group 1 exhibited significantly elevated IL-17 and IL-10 levels compared with the other groups. At 12 months, Group 1 showed persistent IL-1β elevation, whereas Groups 0 and 2 had undetectable levels of this cytokine (P = 0.007). Group 1 also showed higher IL-1α, IL-2, IL-4 and TGF-α levels at 12 months. Network analysis revealed that Group 0 achieved substantial network density reduction, whereas Groups 1 and 2 maintained high connectivity at 12 months. RA patients with near-remission exhibited a distinct inflammatory phenotype characterized by persistent IL-1β elevation and maintained cytokine network density. These findings suggest that patient-reported symptoms in these patients have an inflammatory basis rather than a purely non-inflammatory basis, supporting the importance of achieving stringent Boolean remission and highlighting the need for targeted therapeutic approaches. University Hospital Medical Information Network Clinical Trials Registry; http://www.umin.ac.jp/ctr/; #UMIN000012524.