Plasma calprotectin as a biomarker of ultrasound synovitis in rheumatoid arthritis patients receiving IL-6 antagonists or JAK inhibitors

Abstract

Objectives: To analyse the accuracy of plasma calprotectin in patients with rheumatoid arthritis (RA) receiving monoclonal antibodies against IL-6 receptors (anti-rIL-6) or JAK inhibitors (JAKis) in detecting ultrasound (US) synovitis and compare it with acute phase reactants [high-sensitivity C-reactive protein (hs-CRP) and ESR]. Methods: An observational cross-sectional study of RA patients receiving anti-rIL-6 (tocilizumab or sarilumab) or JAKi, (baricitinib or tofacitinib) was made. Plasma calprotectin for the diagnosis of US synovitis [synovial hypertrophy grade (SH) ⩾ 2 plus power Doppler signal (PD) ⩾ 1] was analysed using receiver operating characteristic curves (ROCs). The performance of ESR and hs-CRP was also studied. The three ROC curves were compared to determine which had the highest discriminatory power. Associations between plasma calprotectin and US scores were made using correlation analysis. Results: Sixty-three RA patients were included. Mean plasma calprotectin levels were significantly higher in patients with US synovitis than in those without (0.89 ± 0.85 vs 0.30 ± 0.12 μg/ml; p = 0.0003). A moderate correlation between calprotectin and all US scores (HS score Rho = 0.479; PD score Rho = 0.492; and global score Rho = 0.495) was found. The discriminatory capacity of plasma calprotectin showed an AUC of 0.795 (95% CI: 0.687–0.904). The AUC of hs-CRP and ESR was 0.721 and 0.564, respectively. hs-CRP serum levels showed a low positive correlation with the three US scores (Rho < 0.40). After analysis according to the drugs administered, the correlation disappeared in patients receiving anti-rIL-6. Conclusion: Plasma calprotectin may be a sensitive biomarker of synovial inflammation in RA patients treated with anti-rIL-6 or JAKi.

Neutrophilic activity biomarkers (plasma neutrophil extracellular traps and calprotectin) in established rheumatoid arthritis patients receiving biological or JAK inhibitors: a clinical and ultrasonographic study

“…These results are in line with the existing literature. Previous studies have indicated that this protein re ects a patient's clinical status more accurately than APRs [10][11][12][13], including clinical remission or low disease activity. Furthermore, calprotectin serves as a prognostic biomarker for radiographic progression [50], a marker of therapeutic response to speci c targeted DMARDs (20), and it has proved useful in predicting disease ares in seemingly controlled patients [51].…”

“…Moreover, when secreted into the synovium, calprotectin subsequently enters peripheral blood circulation. Levels of calprotectin in serum or plasma have been found to correlate closely with in ammatory disease activity in RA patients and therefore provide a more accurate re ection of the patient's clinical status than APRs [10][11][12][13].…”

Neutrophilic Activity Biomarkers (Plasma Neutrophil Extracellular Traps and Calprotectin) in Established Patients with Rheumatoid Arthritis Receiving Biological or JAK Inhibitors: A Clinical and Ultrasonographic Study

“…To reduce variation in calprotectin determinations, the whole procedure was performed in a Triturus Autoanalyzer; the coefficients of variation were 5% within and 13% between assays. This technique had already been used by our group for previous studies[ 11 ].…”

“…To ensure strict criteria for defining US synovitis, only patients with SH grade ≥ 2 plus PD signal ≥ 1 were considered to have active synovitis [ 37 ]. This US assessment method had been previously employed in prior studies conducted by our group [ 11 ]. Clinically symptomatic joints were also evaluated to assess whether US synovitis was present.…”

Calprotectin in Patients with Rheumatic Immunomediated Adverse Effects Induced by Checkpoints Inhibitors

“…Increased calprotectin expression has also been found in patients with rheumatic diseases [20]. In rheumatoid arthritis (RA) patients, serum and plasma calprotectin levels are sensitive markers of inflammation [21,22] and have been associated with radiographic damage [23]. In addition, calprotectin can be a biomarker of clinical responses to antirheumatic drugs [24] and a predictive factor for disease relapse [25].…”