Pos0480 ultrasound synovitis and neutrophilic activity markers (plasma calprotectin and neutrophil extracellular traps) in rheumatoid arthritis patients receiving biological or jak inhibitors

Background Studies have shown an association between active synovitis measured by ultrasound (US) with plasma calprotectin in rheumatoid arthritis (RA) patients [1]. Neutrophil extracellular traps (NETs) may play a pathogenetic role in RA [2]. Elevated plasma NETs have been observed in RA patients, although their association with disease activity is unclear. No studies have analyzed the association between NETs remnants and US synovitis in RA Objectives To analyse whether plasma calprotectin and NETs remnants are associated with synovial inflammation measured by US in patients with established RA treated with biological therapies or JAK inhibitors (JAKi). Methods Observational cross-sectional study. RA patients (ACR/EULAR 2010) receiving treatment with biologic DMARDs (IL6 inhibitors (IL6i), TNF inhibitors (antiTNF), rituximab (RTX)) or JAKi) were consecutively included regardless of disease activity and previous therapy. Clinical disease activity indexes and laboratory parameters of inflammation were evaluated. Plasma calprotectin was analysed. Plasma levels of elastase-DNA (EN-DNA) and histone-DNA complex (H 3 -DNA) (NETs remnants) were examined using a home-made ELISA test. Joint US of both hands was evaluated and graded according to Szudlarek’s score. The synovial hypertrophy (SH), power Doppler (PD) and the total score (SH+PD) was calculated. US active synovitis as previously defined (3) was calculated (SH ≥ 2 + PD ≥1). A correlation study between neutrophilic markers and US scores was made. Results 101 RA patients (91% female, 86% seropositive (RF and/or ACPA) were included. Mean age was 55.4 ±12.1 yrs and the mean RA duration was 15.4 ±9.5 yrs. 78 received treatment with biologics (45 IL6i, 30 antiTNF and 3 RTX) and 23 JAKi. Mean DAS28, CDAI and SDAI were 3.19, 12 and 13 respectively. Low disease activity or remission (CDA<10) were found in 56 patients (54.5%). Mean total US score was 12.7 ±13.7 and US active synovitis was found in 69 patients (69.8%). Means levels of plasma calprotectin were 0.98 μg/ml ±1.4 and plasma NETs remnants were 1.1 ±0.4 (EN-DNA) and 0.9 ±0.08(H3-DNA) [Table 1]. Plasma NETs remnants were not correlated with any US scores. Calprotectin correlated moderately with US scores (ρ between 0.54 and 0.60, p<0.001). There was no correlation between both NETs remnants and calprotectin levels. Mean calprotectin levels were significantly higher in patients with US active synovitis (1.28 vs 0.35 μg/ml, p<0.001) but NETs remnants were not (data not shown). The lack of correlation between NETs and US scores was observed in all therapeutic groups. Table 1. Clinical and laboratory characteristics IL6i n 45 JAKi n 23 AntiTNF n 30 RTX n 3 Total n101 Age 56.4±11.3 53.9±12.5 55.4±13.1 50.9±14.3 55.4±12.1 Female 42(93.3) 20 (87) 27(90) 3(100) 92(91.1) Seropositive (ACPA/ RF) 39(86.7) 22(95.7) 23(76.7) 3(100) 101(86.1) Disease duration (years) 16.4±8.1 12.2±9.3 16.5±11.6 14.6±8.5 15.4±9.51 28TJC 4.1±5.8 3.7±5.4 2.3±3.7 14.3±2.1 3.8±5.4 28SJC 1.6±2.3 2.0±2.7 2.2±0.5 9,3±0.5 1.8±2.7 DAS28 2.8±1.2 3.7±1.4 3.1±1.1 6.3±0.6 3.2±1.3 CDAI 12.0±10.6 12.4±9.3 9.9±9.4 40.1±0,8 12.3±10.1 SDAI 12.4±10.7 13.1±9.6 11.03±11.1 42.8±3.08 13.04±11.6 hs PCR (mg/dL) 0.1± 0.2 0.4±0.43 0.7± 2.5 2.3±2.6 0.45±1.4 Plasma calprotectin (μg/ml) 0.73±0.64 0.93±1.02 1.25±2.24 2.47±1.45 0.98±1.45 EN-DNA 1.1±0.4 1.1±0.3 1,1±0.6 0,9±0.1 1.1±0.4 H 3 -DNA 1.1±0.3 1.1±0.2 1,1±0.2 0,8±0.5 1.1±0.4 SH score 6.20±5.6 7.6±7.6 6.83±6.6 32.7±8.1 7.5±7.8 PD score 4.9±5.0 5.0±6.1 4.35±6.0 20.0±10.5 5.2±6.2 Total US score 11.1±10.3 12.6±13.4 11.1±12.4 52.7±15.8 12.7±13.6 Results are mean ±standard deviation or number of patients (%) Conclusion Plasma calprotectin but not NET remnants were associated with synovial inflammation measured by US in established RA patients receiving biologic or JAKi therapy. The two markers may play a different pathogenetic role in RA. References [1]Frade- Sosa.Ther Adv Musculoskelet Dis 2022. [2]Song Frontiers in Immunology 2021. [3]Ramirez Arthritis Res Ther 2014 Acknowledgements: NIL. Disclosure of Interests None Declared.