Browsing by Author "Gonçalves, Raquel"
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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.
- 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.
- Development and validation of risk matrices for Crohn's Disease outcomes in patients who underwent early therapeutic interventionsPublication . Dias, Cláudia Camila; Rodrigues, Pedro Pereira; Coelho, Rosa; Santos, Paula Moura; Fernandes, Samuel; Lago, Paula; Caetano, Cidalina; Rodrigues, Angela; Portela, Francisco; Oliveira, Ana; Ministro, Paula; Cancela, Eugenia; Vieira, Ana Isabel; Barosa, Rita; Cotter, Jose; Carvalho, Pedro; Cremers, Isabelle; Trabulo, Daniel; Caldeira, Paulo; Antunes, Artur; Rosa, Isadora; Moleiro, Joana; Peixe, Paula; Herculano, Rita; Gonçalves, Raquel; Gonçalves, Bruno; Sousa, Helena Tavares; Contente, Luis; Morna, Henrique; Lopes, Susana; Magro, FernandoIntroduction: The establishment of prognostic models for Crohn's disease [CD] is highly desirable, as they have the potential to guide physicians in the decision-making process concerning therapeutic choices, thus improving patients' health and quality of life. Our aim was to derive models for disabling CD and reoperation based solely on clinical/demographic data. Methods: A multicentric and retrospectively enrolled cohort of CD patients, subject to early surgery or immunosuppression, was analysed in order to build Bayesian network models and risk matrices. The final results were validated internally and with a multicentric and prospectively enrolled cohort. Results: The derivation cohort included a total of 489 CD patients [64% with disabling disease and 18% who needed reoperation], while the validation cohort included 129 CD patients with similar outcome proportions. The Bayesian models achieved an area under the curve of 78% for disabling disease and 86% for reoperation. Age at diagnosis, perianal disease, disease aggressiveness and early therapeutic decisions were found to be significant factors, and were used to construct user-friendly matrices depicting the probability of each outcome in patients with various combinations of these factors. The matrices exhibit good performance for the most important criteria: disabling disease positive post-test odds = 8.00 [2.72-23.44] and reoperation negative post-test odds = 0.02 [0.00-0.11]. Conclusions: Clinical and demographical risk factors for disabling CD and reoperation were determined and their impact was quantified by means of risk matrices, which are applicable as bedside clinical tools that can help physicians during therapeutic decisions in early disease management.
- Impact of early surgery and immunosuppression on Crohn's disease disabling outcomesPublication . Magro, Fernando; Dias, Cláudia C.; Coelho, Rosa; Santos, Paula M.; Fernandes, Samuel; Caetano, Cidalina; Rodrigues, Angela; Portela, Francisco; Oliveira, Ana; Ministro, Paula; Cancela, Eugenia; Vieira, Ana I.; Barosa, Rita; Cotter, Jose; Carvalho, Pedro; Cremers, Isabelle; Trabulo, Daniel; Caldeira, Paulo; Antunes, Artur; Rosa, Isadora; Moleiro, Joana; Peixe, Paula; Herculano, Rita; Gonçalves, Raquel; Gonçalves, Bruno; Sousa, Helena Tavares; Contente, Luis; Morna, Henrique; Lopes, SusanaBackground and Aims: The definition of early therapeutic strategies to control Crohn's disease aggressiveness and prevent recurrence is key to improve clinical practice. This study explores the impact of early surgery and immunosuppression onset in the occurrence of disabling outcomes. Methods: This was a multicentric and retrospective study with 754 patients with Crohn's disease, who were stratified according to the need for an early surgery (group S) or not (group I) and further divided according to the time elapsed from the beginning of the follow-up to the start of immunosuppression therapy. Results: The rate of disabling events was similar in both groups (S: 77% versus I: 76%, P = 0.700). The percentage of patients who needed surgery after or during immunosuppression therapy was higher among group S, both for first surgeries after the index event (38% of groups S versus 21% of group I, P, 0.001) and for reoperations (38% of groups S versus 12% of group I, P < 0.001). The time elapsed to reoperation was shorter in group I (HR = 2.340 [1.367-4.005]), stratified for the onset of immunosuppression. Moreover, reoperation was far more common among patients who had a late start of immunosuppression (S-36: 50% versus S0-6: 27% and S6-36: 25%, P < 0.001) and (I-36: 16% versus I0-6: 5% and I6-36: 7%, P, 0.001). Conclusions: Although neither early surgery nor immunosuppression seem to be able to prevent global disabling disease, an early start of immunosuppression by itself is associated with fewer surgeries and should be considered in daily practice as a preventive strategy.
- The who-when-why triangle of complementary and alternative medicine use among Portuguese IBD patientsPublication . Portela, Francisco; Dias, Camila C.; Caldeira, Paulo; Cravo, Marilia; Deus, João; Gonçalves, Raquel; Lago, Paula; Morna, Henrique; Peixe, Paula; Ramos, Jaime; Sousa, Helena Tavares; Tavares, Lurdes; Vasconcelos, Helena; Magro, Fernando; Ministro, PaulaBackground: The use of complementary and alternative medicines is increasing among chronic patients, particularly those afflicted with inflammatory bowel diseases. Aim: This study aimed to address the prevalence of complementary and alternative medicines use among Portuguese inflammatory bowel diseases' patients. Methods: Patients were invited to fill an anonymous questionnaire concerning the use of complementary and alternative medicines. Results: Thirty-one per cent of the patients reported having used complementary and alternative medicines in the past, whereas 12% were using them by the time the questionnaire was administered. Fifty-nine per cent of the users did not share this information with their physician, whereas 14% and 8% discontinued their medication and periodical examination, respectively. Steroids prescription (OR = 2.880) and a higher instruction level (OR = 3.669) were predictors of complementary and alternative medicines use in this cohort. Conclusions: Roughly a third of Portuguese IBD patients had used CAM. Steroid treatment and an academic degree are associated with CAM use. Given the potential side effects and interactions, patient information about the benefits and limitations of conventional and complementary treatments should be reinforced. (C) 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
- Transmural remission improves clinical outcomes up to 5 years in Crohn's diseasePublication . Fernandes, Samuel Raimundo; Serrazina, Juliana; Botto, Inês Ayala; Leal, Tiago; Guimarães, Andreia; Garcia, Joana Lemos; Rosa, Isadora; Prata, Rita; Carvalho, Diana; Neves, João; Campelo, Pedro; Ventura, Sofia; Silva, Andrea; Coelho, Mariana; Sequeira, Cristiana; Oliveira, Ana Paula; Portela, Francisco; Ministro, Paula; Sousa, Helena Tavares; Ramos, Jaime; Claro, Isabel; Gonçalves, Raquel; Correia, Luís Araújo; Marinho, Rui Tato; Cortez‐Pinto, Helena; Magro, FernandoIntroductionEvidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. MethodsMulticenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR). Results20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR. ConclusionsTR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.