Abstract
ObjectiveClinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation.MethodsSeventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0–1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves.ResultsThe total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58–67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity.ConclusionThe present study demonstrates the potential of calprotectin to distinguish RA patients in both clinical and ultrasound-defined remission from patients in clinical remission but with residual subclinical disease activity.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterised by persistent symmetric synovitis, the development of joint deformities and bone destruction
Disease activity was assessed by the DAS28 score, which includes the swollen joint count (SJC) and tender joint count (TJC), the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) and the patient’s and physician’s global assessment of activity on the visual analogue scale (VAS), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) [30,31,32]
Fifty-two patients were being treated with methotrexate, three patients were being treated with sulfasalazine and five patients were being treated with leflunomide
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterised by persistent symmetric synovitis, the development of joint deformities and bone destruction. The introduction of new drugs and strategies, more accurate assessments of joint inflammation and tighter control of disease activity have markedly increased rates of clinical remission [1, 2]. It has been demonstrated that some patients who are in clinical remission may experience functional worsening and radiographic progression [4,5,6]. Recent data clearly showed that the use of sensitive imaging techniques (e.g., magnetic resonance imaging or ultrasonography) permits the detection of residual subclinical disease activity despite clinical remission, which may explain continuing structural progression [7, 8]. Some patients in clinical remission do not have a lack of joint inflammation; rather, they have low disease activity that is not detectable by clinical examination or conventional laboratory tests [9]. More accurate methods for evaluating remission status are needed
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