C-reactive protein in Crohn’s disease: how informative is it?

Magro, Fernando; Sousa, Paula; Ministro, Paula

doi:10.1586/17474124.2014.893821

Cited by 22 publications

(18 citation statements)

References 96 publications

(150 reference statements)

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“…Previous analyses examining associations between certolizumab pegol concentrations and Crohn's disease activity index had mixed results . Objective markers of inflammation and severity of Crohn's disease include C‐reactive protein and faecal calprotectin, which have been associated with disease activity and endoscopic healing . Specifically, faecal calprotectin values of ≤ 250 μg/g are indicative of endoscopic remission .…”

Section: Discussionmentioning

confidence: 99%

Exposure‐response relationship of certolizumab pegol induction and maintenance therapy in patients with Crohn's disease

Casteele

Feagan

Vermeire

et al. 2017

Aliment Pharmacol Ther

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SummaryBackgroundTherapeutic drug monitoring may optimize therapy for Crohn's disease (CD).AimTo use a population pharmacokinetic model that accounts for the time‐varying nature of covariates to simulate certolizumab pegol (CZP) concentrations to evaluate the exposure‐response relationship for CZP in Crohn's disease.MethodsAdults (N = 2157) with Crohn's disease were treated with CZP in nine clinical trials. Simulated CZP concentrations were compared to outcomes at weeks 6 and 26, including Crohn's disease activity index (CDAI) response (decrease from baseline ≥ 100 points), remission (CDAI ≤ 150), C‐reactive protein (CRP) ≤ 5 mg/L, faecal calprotectin (FC) ≤ 250 μg/g, and a composite endpoint of CDAI ≤ 150 and FC ≤ 250 μg/g. Multivariable analyses identified covariates associated with outcomes and receiver operating characteristic analyses determined optimal CZP concentrations.Results CZP concentrations at weeks 2, 4 and 6 were higher in patients with clinical response, remission, CRP ≤ 5 mg/L or FC ≤ 250 μg/g at week 6 than without. In multivariable analyses, higher CZP concentrations at week 6 were associated with the composite outcome at weeks 6 and 26 (P < .001). Although the exposure‐response relationship varied among patients, approximate CZP concentrations of at least 36.1 μg/mL (positive predictive value [PPV] 22.8% and negative predictive value [NPV] 92.7%) and at least 14.8 μg/mL (PPV 28.0% and NPV 90.4%) at weeks 6 and 12 were associated with weeks 6 and 26 outcomes.ConclusionsAn exposure‐response relationship was apparent for CZP in Crohn's disease and achieving higher CZP concentrations may increase the likelihood of attaining efficacy outcomes, but this remains to be evaluated prospectively.

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Section: Discussionmentioning

confidence: 99%

Exposure‐response relationship of certolizumab pegol induction and maintenance therapy in patients with Crohn's disease

Casteele

Feagan

Vermeire

et al. 2017

Aliment Pharmacol Ther

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“…5 CRP is a serologic acute-phase marker, and objective measures of inflammation in CD. 6,7 Compared with clinical disease activity index, CRP is considered to be more useful in terms of evaluating the severity of inflammatory activity 8 and is used to assess the clinical treatment by observing the changes of CRP level in numerous studies. 9–11 …”

Section: Introductionmentioning

confidence: 99%

Can Dynamic Contrast-Enhanced MRI (DCE-MRI) and Diffusion-Weighted MRI (DW-MRI) Evaluate Inflammation Disease

et al. 2016

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The aim of the study was to investigate diagnosis efficacy of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI) in Crohn's disease (CD). To find out the correlations between functional MRI parameters including Ktrans, Kep, Ve, Vp, and apparent diffusion coefficient (ADC) with a serologic biomarker. The relationships between pharmacokinetic parameters and ADC were also studied.Thirty-two patients with CD (22 men, 10 women; mean age: 30.5 years) and 18 healthy volunteers without any inflammatory disease (10 men, 8 women; mean age, 34.11 years) were enrolled into this approved prospective study. Pearson analysis was used to evaluate the correlation between Ktrans, Kep, Ve, Vp, and C-reactive protein (CRP), ADC, and CRP respectively. The diagnostic efficacy of the functional MRI parameters in terms of sensitivity and specificity were analyzed by receiver operating characteristic (ROC) curve analyses. Optimal cut-off values of each functional MRI parameters for differentiation of inflammatory from normal bowel were determined according to the Youden criterion.Mean value of Ktrans in the CD group was significantly higher than that of normal control group. Similar results were observed for Kep and Ve. On the contrary, the ADC value was lower in the CD group than that in the control group. Ktrans and Ve were shown to be correlated with CRP (r = 0.725, P < 0.001; r = 0.533, P = 0.002), meanwhile ADC showed negative correlation with CRP (r = −0.630, P < 0.001). There were negative correlations between the pharmacokinetic parameters and ADC, such as Ktrans to ADC (r = −0.856, P < 0.001), and Ve to ADC (r = −0.451, P = 0.01). The area under the curve (AUC) was 0.994 for Ktrans (P < 0.001), 0.905 for ADC (P < 0.001), 0.806 for Ve (P < 0.001), and 0.764 for Kep (P = 0.002). The cut-off point of the Ktrans was found to be 0.931 min–1. This value provided the best trade-off between sensitivity (93.8%) and specificity (100%). The best cut-off point of ADC was 1.11 × 10–3 mm2/s. At this level, sensitivity was 100% and specificity was 68.8%.DCE-MRI and DW-MRI were helpful in the diagnosis of CD. Quantitative MRI parameters could be used to assess the severity of inflammation. The relationships between pharmacokinetic parameters (Ktrans and Ve) and ADC reflected microstructure and microcirculation of CD to some extent.

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“…9/13 patients who completed PET scanning both at baseline and a median [range] of 12 [11][12][13][14][15][16][17][18] weeks after initiation of anti-TNF treatment had favourable clinical responses 27 (median [range] responder ΔHBI = 5 [3][4][5][6][7][8][9]; non-responder ΔHBI = 1[-1-2]), (Table 1). …”

Section: Contrasting Fdg-pet Measures In Responders Versus Non-responmentioning

confidence: 99%

“…Table 6 4 Test-retest repeatability 5 patients (1 female) with active CD were recruited for this arm of the study, and 4 completed the two scans within a median [range] period of 7 [4][5][6][7][8][9][10][11][12] days. The repeatability of the PET measures were estimated in segments with a signal focus > LivSUVMEAN (Table 7).…”

Section: Responsiveness Ratiosmentioning

confidence: 99%

“…Biomarkers currently in use in clinical practice (e.g., C-reactive protein [CRP] and faecal calprotectin) lack sensitivity and specificity 5,4 . Recently, imaging biomarkers, such as the Magnetic Resonance Index of Activity (MaRIA) have been validated against colonoscopy as a measure of mucosal and transmural disease load in cross sectional studies [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

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Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohnʼs Disease

Russo¹,

Khan

Janisch

et al. 2016

Inflammatory Bowel Diseases

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C-reactive protein in Crohn’s disease: how informative is it?

Cited by 22 publications

References 96 publications

Exposure‐response relationship of certolizumab pegol induction and maintenance therapy in patients with Crohn's disease

Exposure‐response relationship of certolizumab pegol induction and maintenance therapy in patients with Crohn's disease

Can Dynamic Contrast-Enhanced MRI (DCE-MRI) and Diffusion-Weighted MRI (DW-MRI) Evaluate Inflammation Disease

Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohnʼs Disease

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