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Cytokine/chemokine profiles in rheumatoid arthritis patients who failed Boolean remission solely due to elevated patient global assessment
Objective: 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.
Methods: 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.
Results: At baseline, Group 1...
Show moreObjective: 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.
Methods: 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.
Results: 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-1 beta elevation, whereas Groups 0 and 2 had undetectable levels of this cytokine (P = 0.007). Group 1 also showed higher IL-1 alpha, IL-2, IL-4 and TGF-alpha 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.
Conclusion: RA patients with near-remission exhibited a distinct inflammatory phenotype characterized by persistent IL-1 beta 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.
Trial registration: University Hospital Medical Information Network Clinical Trials Registry; http://www.umin.ac.jp/ctr/; #UMIN000012524.
Show less- All authors
- Fukui, S.; Michitsuji, T.; Endo, Y.; Nishino, A.; Furukawa, K.; Shimizu, T.; Umeda, M.; Sumiyoshi, R.; Koga, T.; Iwamoto, N.; Tamai, M.; Origuchi, T.; Schie, K.A. van; Ueki, Y.; Eiraku, N.; Yoshitama, T.; Matsuoka, N.; Suzuki, T.; Okada, A.; Hamada, H.; Ayano, M.; Hidaka, T.; Tsuru, T.; Huizinga, T.W.J.; Toes, R.E.M.; Kawakami, A.; Kawashiri, S.Y.
- Date
- 2026-02-01
- Journal
- Rheumatology
- Volume
- 65
- Issue
- 2