Calprotectin more accurately discriminates the disease status of rheumatoid arthritis patients receiving tocilizumab than acute phase reactants

Inciarte-Mundo, J.; Ruíz-Esquide, Virginia; Hernández, M. Victoria; Cañete, Juan D.; Cabrera-Villalba, S.; Ramírez, Julio; Yagüe, Jordi; Sanmarti, Raimón

doi:10.1093/rheumatology/kev251

Cited by 29 publications

(41 citation statements)

References 16 publications

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“…We recently demonstrated that calprotectin is a more accurate biomarker than CRP level or ESR for the assessment of disease activity in RA patients receiving tocilizumab, a biologic agent with a dramatic impact on APR due to its blocking of IL-6, which may lead to an overestimate of the rates of response when using composite indices that include the acute-phase response, such as the DAS or SDAI (26). Therefore, calprotectin emerges as a biomarker that more accurately stratifies disease activity than the APRs in RA patients receiving biologic therapy, irrespective of the mechanism of action (inhibition of TNF or IL-6).…”

Section: Discussionmentioning

confidence: 99%

“…Third, the cutoff point of calprotectin associated with remission or low disease activity in RA should be interpreted with caution and merits further investigation in studies with a larger sample size in order to establish the clinical significance. A higher cutoff of calprotectin levels was found in patients treated with tocilizumab (26). Fourth, the clinical value of calprotectin measurements in individual patients is hampered by some overlap values between patients with different degrees of disease activity.…”

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confidence: 98%

“…After 3 washes and the addition of the enzyme 45 substrate, the optical density values at 405 nm were determined using an ELISA reader. To reduce variation in calprotectin determination, the whole procedure was performed in a Triturus autoanalyzer (26). ESR was measured using the Westergren method (normal value [NV] ,20 mm/ hour), and CRP level by nephelometry (lowest detection limit of 0.01 mg/dl; NV ,0.8 mg/dl).…”

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confidence: 99%

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Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

Inciarte-Mundo

Hernández

Ruíz-Esquide

et al. 2016

Arthritis Care & Research

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Objective. To compare the accuracy of serum calprotectin and acute-phase reactants (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels. Methods. We conducted a cross-sectional study of 87 RA patients receiving adalimumab, etanercept (ETN), or infliximab (IFX); 56 psoriatic arthritis (PsA) patients and 40 healthy blood donors were included as controls. Associations between calprotectin, CRP, and ESR and composite articular indices (Disease Activity Score in 28 joints [DAS28], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index) were analyzed by correlation and linear regression and the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves (area under the curve [AUC]). Results. Calprotectin levels correlated better with all composite activity indices than CRP and ESR (all r coefficients >0.70). Calprotectin levels were significantly lower in RA and PsA patients in clinical remission compared with those with low disease activity for all articular indices. In RA, ESR discriminated between remission and low disease activity only when using DAS28, and CRP only with SDAI. In RA patients in remission/low disease activity, calprotectin but not CRP or ESR distinguished between patients with no swollen joints and those with ‡1 swollen joint (1.74 mg/ml versus 3.04 mg/ml; P 5 0.010). Using DAS28 ‡2.6 as the reference variable, calprotectin showed an AUC of 0.92; the best cutoff was ‡2.47 mg/ml with a likelihood ratio of 6.3 (95% confidence interval 2.5-15.8). Calprotectin serum levels inversely correlated with trough serum drug levels of ETN (r 5 20.671, P < 0.001) and IFX (r 5 20.729, P 5 0.017). Conclusion. Calprotectin may more accurately discriminate disease activity in RA patients receiving TNFi than acutephase reactants, even in patients with low inflammatory activity.

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confidence: 99%

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Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

Inciarte-Mundo

Hernández

Ruíz-Esquide

et al. 2016

Arthritis Care & Research

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“…23 CLP correlates with inflammatory indices, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum amyloid A protein (SAA) and inversely with TNF-a inhibitors through levels. 74,76,77 CLP serum levels seem to perform even better compared to CRP and ESR. In fact, CLP has showed to correlate better with all clinical indices, such as 28 joint-disease activity score and simplified disease activity index.…”

Section: Clp In Rheumatic Diseasesmentioning

confidence: 95%

“…67 CLP serum levels correlate with disease activity and are associated with markers of more severe RA in many studies. 48,49,61,64,66,[68][69][70][71][72][73][74][75][76] CLP has been found to be higher in the serum of rheumatoid factor 48,49,69,70,71,73 and anticitrullinated peptide positive patients 23,49,64,72 compared with seronegative ones. 23 CLP correlates with inflammatory indices, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum amyloid A protein (SAA) and inversely with TNF-a inhibitors through levels.…”

Section: Clp In Rheumatic Diseasesmentioning

confidence: 99%

Calprotectin in rheumatic diseases

Ometto

Friso

Astorri

et al. 2016

Exp Biol Med (Maywood)

139

105

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Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment. AbstractCalprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-a inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker.

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Analytical and clinical evaluation of DiaSorin Liaison® Calprotectin fecal assay adapted for serum samples

Macías-Muñoz

Frade‐Sosa

Iniciarte-Mundo

et al. 2022

Clinical Laboratory Analysis

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Calprotectin more accurately discriminates the disease status of rheumatoid arthritis patients receiving tocilizumab than acute phase reactants

Abstract: Calprotectin serum levels seem to be an accurate biomarker for assessing disease activity in RA patients receiving TCZ.

Cited by 29 publications

References 16 publications

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

Calprotectin in rheumatic diseases

Analytical and clinical evaluation of DiaSorin Liaison® Calprotectin fecal assay adapted for serum samples

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