ABSTRACT
OBJECTIVES: The objective of this study was to assess the prevalence of ultrasound (US) abnormalities and association with clinical parameters in rheumatoid arthritis (RA) clinical remission. METHODS: Patients with established RA in clinical remission (DAS28-CRP < 2.4) taking conventional synthetic disease-modifying anti-rheumatic drugs were recruited as part of the Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study. In addition, patients from the Newcastle Early Arthritis Clinic (NEAC) with early active RA (DAS28-CRP > 2.4) or seronegative non-inflammatory arthralgia (NIA) were studied as positive and negative controls, respectively. The association between individual dependent variables (synovial power Doppler and greyscale, tenosynovial greyscale, and erosions) and clinical parameters was assessed by multivariate ordinal logistic regression, with adjustment for multiple testing. RESULTS: A total of 294 patients were included: 66 RA in remission, 146 active RA, and 82 NIA. Within the active RA group, significant associations were observed between swollen joint count and higher total synovial greyscale score (OR 1.17 95% CI 1.08-1.26, p < 0.001) and higher total synovial power Doppler score (OR 1.20, 95% CI 1.12-1.30, p < 0.001). No significant associations were observed for the NIA group. In the RA remission group, US abnormalities were frequently observed and comparable for both DAS28-CRP and 2011 ACR/EULAR Boolean remission, with no significant association with clinical parameters identified. CONCLUSION: We observed widespread subclinical US findings in RA patients in clinical remission, even when remission is defined using the stringent ACR/EULAR Boolean criteria. In contrast to active disease, synovial power Doppler failed to show significant association with any of the clinical parameters in RA remission. Our results suggest that clinical and US examinations are non-overlapping in evaluating RA remission, challenging the proposition of US-driven management strategies in this setting.
ABSTRACT
BACKGROUND: Many patients with rheumatoid arthritis (RA) achieve disease remission with modern treatment strategies. However, having achieved this state, there are no tests that predict when withdrawal of therapy will result in drug-free remission rather than flare. We aimed to identify predictors of drug-free remission in RA. METHODS: The Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study was a unique, prospective, interventional cohort study of complete and abrupt cessation of conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA of at least 12 months duration and in clinical and ultrasound remission discontinued DMARDs and were monitored for six months. The primary outcome was time-to-flare, defined as disease activity score in 28 joints with C-reactive protein (DAS28-CRP)â¯≥â¯2.4. Baseline clinical and ultrasound measures, circulating inflammatory biomarkers, and peripheral CD4+ T cell gene expression were assessed for their ability to predict time-to-flare and flare/remission status by Cox regression and receiver-operating characteristic (ROC) analysis respectively. RESULTS: 23/44 (52%) eligible patients experienced an arthritis flare after a median (IQR) of 48 (31.5-86.5) days following DMARD cessation. A composite score incorporating five baseline variables (three transcripts [FAM102B, ENSG00000228010, ENSG00000227070], one cytokine [interleukin-27], one clinical [Boolean remission]) differentiated future flare from drug-free remission with an area under the ROC curve of 0.96 (95% CI 0.91-1.00), sensitivity 0.91 (0.78-1.00) and specificity 0.95 (0.84-1.00). CONCLUSION: We provide proof-of-concept evidence for predictors of drug-free remission in RA. If validated, these biomarkers could help to personalize immunosuppressant withdrawal: a therapy paradigm shift with ensuing patient and economic benefits.