Calprotectin and TNF trough serum levels identify power Doppler ultrasound synovitis in rheumatoid arthritis and psoriatic arthritis patients in remission or with low disease activity

Abstract

BackgroundSerum levels of calprotectin, a major S100 leucocyte protein, are associated with disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Higher drug trough serum levels are associated with good response in patients treated with tumour necrosis factor inhibitors (TNFi). Power Doppler ultrasound (PDUS) synovitis is predictive of flare and progression of structural damage in patients in clinical remission. The purpose of this study was to analyse the accuracy of calprotectin and TNFi trough serum levels in detecting PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity who were receiving TNFi.MethodsWe conducted a cross-sectional study of 92 patients (42 with RA, 50 with PsA) receiving adalimumab (ADA), etanercept (ETN) or infliximab who were in remission or had low disease activity (28-joint Disease Activity Score based on erythrocyte sedimentation rate <3.2). Associations of calprotectin, TNFi trough serum levels and acute phase reactants with PDUS synovitis were assessed using correlation and linear regression analyses. The accuracy and discriminatory capacity in detecting PDUS synovitis was assessed using ROC curves.ResultsPDUS synovitis was found in 62.4 % of RA patients and 32 % of PsA patients. Both RA and PsA patients with PDUS synovitis had higher calprotectin levels and lower TNFi trough serum levels. Calprotectin positively correlated with ultrasound scores (all r coefficients >0.50 in RA). Calprotectin correlated with the PDUS synovitis score in patients treated with ADA and ETN. Using PDUS synovitis (yes or no) as the reference variable, calprotectin had an AUC of 0.826. The best cut-off was ≥1.66 μg/ml, with a likelihood ratio of 2.77. C-reactive protein (AUC 0.673) and erythrocyte sedimentation rate (AUC 0.731) had a lower discriminatory capacity. TNFi trough serum levels were significantly associated with PDUS synovitis (OR 0.67, 95 % CI 0.52–0.85, p < 0.001) but their accuracy (AUC <0.5) was less than that of calprotectin. TNFi trough serum levels were inversely correlated with calprotectin and PDUS synovitis in RA and PsA patients receiving ADA and ETN.ConclusionsCalprotectin and TNFi trough serum levels may help identify PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity.

Serum Calprotectin Discriminates Subclinical Disease Activity from Ultrasound-Defined Remission in Patients with Rheumatoid Arthritis in Clinical Remission

“…However, it is important to note that CRP forms part of the DAS-CRP and SDAI constructs, and patients satisfying the remission criteria defined by these indexes are inherently those in whom CRP failed to discriminate US-detected subclinical inflammation. Our results are in line with those published recently by Inciarte-Mundo et al who had investigated levels of serum calprotectin and its ability to identify PD synovitis in patients with RA and psoriatic arthritis in clinical remission and low disease activity treated by antiTNFα agents [28]. In contrast to above mentioned study, we have focused here more strictly only on patients in clinical remission.…”

“…Thus, we suggested that calprotectin and musculoskeletal ultrasonography might provide more reliable tools for evaluating joint inflammatory activity in RA patients. In line with our hypothesis, Inciarte-Mundo et al [28] have recently demonstrated that calprotectin and TNF trough serum levels may help to identify power Doppler ultrasound synovitis in biologic-treated patients with RA and psoriatic arthritis in remission or low disease activity.…”

Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis

“…Serum and plasma levels of calprotectin are associated with ultrasound assessments of RA disease activity,9 23 25 and elevated levels of calprotectin may indicate sustained inflammation in patients in remission or low disease activity according to DAS28 31…”

Calprotectin in rheumatic diseases

“…72 A recent study by Inciarte-Mundo et al 84 showed that CLP was associated with synovitis at the ultrasonography assessment in RA and psoriatic arthritis (PSA) patients in remission. CLP serum levels had the highest discriminatory capacity compared to CRP and ESR and a cut-off of 1.66 mg/ml for synovitis presence was also identified.…”

“…CLP serum levels had the highest discriminatory capacity compared to CRP and ESR and a cut-off of 1.66 mg/ml for synovitis presence was also identified. 84 Notably, CLP is the only biomarker which has been shown to correlate with radiographic scores 48,49 and there is some evidence that baseline CLP might be predictive of radiographic damage. 48,49,85 In a recent study by Vogl et al, 86 CLP was tested as a marker of inflammation in a murine model of arthritis by optical molecular imaging.…”