IV. Entidades Cooperantes
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Browsing IV. Entidades Cooperantes by Author "Afonso, Joana"
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- Accuracy of faecal calprotectin and neutrophil Gelatinase B-associated Lipocalin in evaluating subclinical inflammation in UlceRaTIVE colitis-the ACERTIVE studyPublication . Magro, Fernando; Lopes, Susana; Coelho, Rosa; Cotter, Jose; Castro, Francisca Dias de; Sousa, Helena Tavares; Salgado, Marta; Andrade, Patrícia; Vieira, Ana Isabel; Figueiredo, Pedro; Caldeira, Paulo; Sousa, A.; Duarte, Maria A.; Avila, Filipa; Silva, João; Moleiro, Joana; Mendes, Sofia; Giestas, Silvia; Ministro, Paula; Sousa, Paula; Gonçalves, Raquel; Gonçalves, Bruno; Oliveira, Ana; Chagas, Cristina; Torres, Joana; Dias, Claudia Camila; Lopes, Joanne; Borralho, Paula; Afonso, Joana; Geboes, Karel; Carneiro, FátimaBackground and Aims: Mucosal healing and histological remission are different targets for patients with ulcerative colitis, but both rely on an invasive endoscopic procedure. This study aimed to assess faecal calprotectin and neutrophil gelatinase B-associated lipocalin as biomarkers for disease activity in asymptomatic ulcerative colitis patients. Methods: This was a multicentric cross-sectional study including 371 patients, who were classified according to their endoscopic and histological scores. These results were evaluated alongside the faecal levels of both biomarkers. Results: Macroscopic lesions [i.e. endoscopic Mayo score >= 1] were present in 28% of the patients, and 9% had active disease according to fht Ulcerative Colitis Endoscopic Index of Severity. Moreover, 21% presented with histological inflammation according to the Geboes index, whereas 15% and 5% presented with focal and diffuse basal plasmacytosis, respectively. The faecal levels of calprotectin and neutrophil gelatinase B-associated lipocalin were statistically higher for patients with endoscopic lesions and histological activity. A receiver operating characteristic-based analysis revealed that both biomarkers were able to indicate mucosal healing and histological remission with an acceptable probability, and cut-off levels of 150-250 mu g/g for faecal calprotectin and 12 mu g/g for neutrophil gelatinase B-associated lipocalin were proposed. Conclusions: Faecal calprotectin and neutrophil gelatinase B-associated lipocalin levels are a valuable addition for assessment of disease activity in asymptomatic ulcerative colitis patients. Biological levels of the analysed biomarkers below the proposed thresholds can rule out the presence of macroscopic and microscopic lesions with a probability of 75-93%. However, caution should be applied whenever interpreting positive results, as these biomarkers present consistently low positive predictive values.
- Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic EscalationPublication . Magro, Fernando; Afonso, Joana; Lopes, Susana; Coelho, Rosa; Gonçalves, Raquel; Caldeira, Paulo; Lago, Paula; Sousa, Helena Tavares; Ramos, Jaime; Gonçalves, Ana Rita; Ministro, Paula; Rosa, Isadora; Vieira, Ana Isabel; Andrade, Patrícia; Soares, João-Bruno; Carvalho, Diana; Sousa, Paula; Meira, Tania; Lopes, Joanne; Moleiro, Joana; Dias, Cláudia Camila; Falcão, Amilcar; Geboes, Karel; Carneiro, FátimaAlthough infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62 mu g/mL vs. 1.15 mu g/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3 mu g/mL (HR = 0.119, p = 0.010), and increased for patients with fecal calprotectin (FC) level above 250 mu g/g (HR = 9.309, p = 0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation. (C) 2017 The Authors. Published by Elsevier B.V.
- Clinical performance of an infliximab rapid quantification assayPublication . Magro, Fernando; Afonso, Joana; Lopes, Susana; Coelho, Rosa; Gonçalves, Raquel; Caldeira, Paulo; Lago, Paula; Sousa, Helena Tavares; Ramos, Jaime; Gonçalves, Ana Rita; Ministro, Paula; Rosa, Isadora; Meira, Tania; Andrade, Patrícia; Soares, João-Bruno; Carvalho, Diana; Sousa, Paula; Vieira, Ana Isabel; Lopes, Joanne; Dias, Cláudia Camila; Geboes, Karel; Carneiro, FátimaBackground: Therapeutic drug monitoring (TDM)-based algorithms can be used to guide infliximab (IFX) adjustments in inflammatory bowel disease (IBD) patients. This study aimed to explore a rapid IFX-quantification test from a clinical perspective. Methods: This manuscript describes a prospective cohort study involving 110 ulcerative colitis (UC) patients on the maintenance phase of IFX. IFX trough levels were quantified using a rapid quantification assay and a commonly-used reference kit. Results: Irrespective of the assay used to measure IFX, its through levels were statistically different between patients with and without endoscopic remission (Mayo endoscopic score = 0), as well as between patients stratified by their faecal calprotectin (FC) levels. Despite the fact that the two methods correlated well with each other [Spearman's rank correlation coefficient = 0.843, p < 0.001; intraclass correlation coefficients = 0.857, 95% confidence interval (CI): 0.791-0.903], there was a discernible systematic variation; values obtained with the reference kit were on average 2.62 units higher than those obtained with the rapid assay. Notwithstanding, 3 mu g/ml was shown to be an acceptable cut-off to assess endoscopic status and inflammatory burden levels using both assays. The percentage of patients that had a positive outcome when the IFX concentration measured by the rapid assay ranked above 3 mu g/ml was 88% both for a Mayo endoscopic score <= 1 and for an FC concentration <250 mu g/g. Conclusions: Based on this study, we concluded that using the rapid IFX assessment system with a 3 mu g/ml threshold is a reliable alternative to the time-consuming enzyme-linked immunosorbent assays in patients on the maintenance phase of IFX.
- Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levelsPublication . Magro, Fernando; Lopes, Joanne; Borralho, Paula; Lopes, Susana; Coelho, Rosa; Cotter, Jose; de Castro, Francisca Dias; Sousa, Helena Tavares; Salgado, Marta; Andrade, Patricia; Vieira, Ana Isabel; Figueiredo, Pedro; Caldeira, Paulo; Sousa, A.; Duarte, Maria A.; Avila, Filipa; Silva, Joao; Moleiro, Joana; Mendes, Sofia; Giestas, Silvia; Ministro, Paula; Sousa, Paula; Goncalves, Raquel; Goncalves, Bruno; Oliveira, Ana; Rosa, Isadora; Rodrigues, Marta; Chagas, Cristina; Dias, Claudia Camila; Afonso, Joana; Geboes, Karel; Carneiro, FatimaObjective Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems-Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. Design Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients' Mayo Endoscopic Score and FC levels. Result GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. Conclusions GS, NI and RHI histopathological scoring systems are comparable in what concerns patients' stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.
- Detection of anti-infliximab antibodies is impacted by antibody titer, infliximab level and IgG4 antibodies: a systematic comparison of three different assaysPublication . Afonso, Joana; Lopes, Susana; Gonçalves, Raquel; Caldeira, Paulo; Lago, Paula; Sousa, Helena Tavares; Ramos, Jaime; Gonçalves, Ana Rita; Ministro, Paula; Rosa, Isadora; Vieira, Ana Isabel; Coelho, Rosa; Tavares, Patrícia; Soares, João; Sousa, Ana Lúcia; Carvalho, Diana; Sousa, Paula; Silva, João Pereira da; Meira, Tânia; Ferreira, Filipa Silva; Dias, Cláudia Camila; Chowers, Yehuda; Ben-Horin, Shomron; Magro, FernandoBackground: There is scant information on the accuracy of different assays used to measure anti-infliximab antibodies (ADAs), especially in the presence of detectable infliximab (IFX). We thus aimed to evaluate and compare three different assays for the detection of IFX and ADAs and to clarify the impact of the presence of circulating IFX on the accuracy of the ADA assays.Methods: Blood samples from 79 ulcerative colitis (UC) patients treated with infliximab were assessed for IFX levels and ADAs using three different assays: an in-house assay and two commercial kits, Immundiagnostik and Theradiag. Sera samples with ADAs and undetectable levels of IFX were spiked with exogenous IFX and analyzed for ADAs.Results: The three assays showed 81-96% agreement for the measured IFX level. However, the in-house assay and Immundiagnostik assays detected ADAs in 34 out of 79 samples, whereas Theradiag only detected ADAs in 24 samples. Samples negative for ADAs with Theradiag, but ADA-positive in both the in-house and Immundiagnostik assays, were positive for IFX or IgG4 ADAs. In spiking experiments, a low concentration of exogenous IFX (5 mu g/ml) hampered ADA detection with Theradiag in sera samples with ADA levels of between 3 and 10 mu g/ml. In the Immundiagnostik assay detection interference was only observed at concentrations of exogenous IFX higher than 30 mu g/ml. However, in samples with high levels of ADAs (> 25 mu g/ml) interference was only observed at IFX concentrations higher than 100 mu g/ml in all three assays. Binary (IFX/ADA) stratification of the results showed that IFX+/ADA and IFX-/ADAs + were less influenced by the assay results than the double-positive (IFX+/ADAs+) and double-negative (IFX-/ADAs-) combination.Conclusions: All three methodologies are equally suitable for measuring IFX levels. However, erroneous therapeutic decisions may occur when patients show double-negative (IFX-/ADAs) or double-positive (IFX+/ADAs+) status, since agreement between assays is significantly lower in these circumstances.
- Serum dipeptidyl peptidase 4: a predictor of disease activity and prognosis in inflammatory bowel diseasePublication . Pinto-Lopes, Pedro; Afonso, Joana; Pinto-Lopes, Rui; Rocha, Catia; Lago, Paula; Goncalves, Raquel; Sousa, Helena Tavares; Macedo, Guilherme; Dias, Claudia Camila; Magro, FernandoBackground: Serum dipeptidyl peptidase 4 (DPP-4) has drawn particular interest as a biomarker in inflammatory bowel disease (IBD), as this protease inactivates several peptides that participate in the inflammatory cascade. Methods: Two prospectively recruited cohorts consisting of 195 patients (101 had Crohn’s disease [CD] and 94 had ulcerative colitis [UC]) were evaluated using clinical indexes and followed up to assess for treatment escalation. Sixty-eight patients underwent endoscopic evaluation at baseline. In the second cohort of 46 biologically treated patients, treatment response was assessed. Serum DPP-4, C-reactive protein (CRP), and fecal calprotectin levels were quantified at baseline and during follow-up. Results: Median DPP-4 levels were significantly lower in active IBD patients when compared with remitters (CD: 1043 [831–1412] vs 1589 [1255–1956] ng/mL; P < 0.001; UC: 1317 [1058–1718] vs 1798 [1329–2305] ng/mL; P = 0.001) and healthy controls (2175 [1875–3371] ng/mL). In fact, DPP-4 was able to distinguish clinical and endoscopic activity from remission, with areas under the curve (AUC) of 0.81/0.93 (CD) and 0.71/0.79 (UC), along with the need for treatment escalation, with comparable AUCs of 0.79 (CD) and 0.77 (UC). Furthermore, DPP-4 levels were higher in responders to treatment and more pronounced among UC (1467 [1301–1641] vs 1211 [1011–1448] ng/mL; P < 0.001) than CD patients (1385 [1185–1592] vs 1134 [975–1469] ng/mL; P = 0.015). Conclusions: Our results suggest that serum DPP-4 can be used as a noninvasive biomarker of IBD activity and biological treatment response and a predictor of treatment escalation, particularly when combined with other biomarkers.
- Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumabPublication . Magro, Fernando; Lopes, Susana; Silva, Marco; Coelho, Rosa; Portela, Francisco; Branquinho, Diogo; Correia, Luís; Fernandes, Samuel; Cravo, Marília; Caldeira, Paulo; Sousa, Helena Tavares; Patita, Marta; Lago, Paula; Ramos, Jaime; Afonso, Joana; Redondo, Isabel; Machado, Patrícia; Philip, George; Lopes, Joanne; Carneiro, FátimaSuppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab.