Background/Purpose: To search biomarkers of clinical relapse and radiological progression in patients with RA in clinical remission

Methods: RA patients in clinical remission (defined as DAS28-ESR < 2.6 for > 6 months) were selected. Clinical, epidemiological and serological data were analyzed. A MRI of dominant hand and an ultrasound assessment of knees and hands were performed at baseline and at 48 weeks. Serum levels of inflammation and angiogenesis biomarkers were determined by Quantibody® Human Array at baseline and 48 weeks. A synovial biopsy was performed in patients with subclinical synovitis. Patients were followed up for 5 years. Clinical and radiological data (hands and feet X-rays) were collected. Clinical relapse was defined as loss of remission status (DAS28 > 2.6) leading to a therapeutic intervention. Treatment change was defined as the change in csDMARD or biological therapy of RA. Radiographic progression was defined as the change in the SvH index at 5 years >10.47 (SDD).

Results: 60 patients fulfilling ACR 2010 criteria for RA and DAS28< 2.6 were included. 1/3 also met remission criteria for SDAI (33.3%), CDAI (31.6%) and ACR (35%). 78.3% of the patients were women. Mean age was 53 years and the disease duration was 110 months. 81.6% were ACPA +. 26% were taking oral prednisone, 76% DMARDs and 45% biological therapies. At baseline, 67% had PD signal and 48% met a more stringent criteria for subclinical synovitis (UdAS: SH > 2 + PD). After 5 years of follow-up, 44 (73.3%), 11 (18.3%), 9 (15%) and 10 (16.6%) patients remained in remission according to DAS28, SDAI, CDAI and ACR criteria, respectively.   29 patients (48.3%) had flares at any time during the 5 years of follow-up. In the multivariate analysis, the variables that were related to clinical relapse were BMI (OR 1.8 CI 95% 1.2-2.7), TNFalpha levels at baseline (OR 32.4, CI 95% 1.9-546.2), the fisrt year change in CXCL16 levels (OR 1.05 CI 95% 1-1.1) and ESR (OR 2.48 CI 95% 1-6.1). Patients who flared during the follow-up had a significantly higher number of mast cells (p=0.02). Regarding to change in treatment, 20 patients (33.3%) changed DMARDs or biological therapy at any time during the 5 years of follow-up. In the logistic regression analysis, BMI (OR 1.3 CI 95% 1-1.7), biological therapy (OR 24.7 CI 95% 2.3-257.2), progression of erosions by MRI during the first year (OR 1.2, CI 95% 1-1.3) and the rate of progression of calprotectin serum levels during the first year (OR 2.8, CI 95% 1-8.2) were the main factors that predicted the change in baseline therapy after 5 years of follow-up . Finally, only 6 patients (10%) had X-Ray progression according to the SvdH index.  The number of macrophages and T cells in synovial tissue at baseline was much higher in patients with radiological progression. Likewise, the first-year rate of bone edema was significantly higher in patients with structural progression (p = 0.04)

Conclusion: 27% of RA patients lost clinical remission (DAS28) after 5 years of follow-up. BMI, serum TNFa levels, and first-year rate of CXCL16 and VSG levels were predictors of joint flares.  Baseline BMI, use of biological therapy, MRI erosions and calprotectin levels predicted the change of baseline therapy for RA. Only 10% of patients had radiological progression along the study.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/biomarkers-of-clinical-relapse-and-radiological-progression-in-patients-with-rheumatoid-arthritis-in-remission-observational-study-of-5-years-of-follow-up/