ABC-RI
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Àcerca do Centro de Investigação Biomédica do Algarve => ABC-RI
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Percorrer ABC-RI por autor "Afonso, Joana"
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- How many biomarker measurements are needed to predict prognosis in Crohn's disease patients under infliximab?—A prospective studyPublication . Magro, Fernando; Estevinho, Maria Manuela; Catalano, Gaia; Patita, Marta; Arroja, Bruno; Lago, Paula; Rosa, Isadora; Sousa, Helena Tavares; Ministro, Paula; Mocanu, Irina; Vieira, Ana; Castela, Joana; Moleiro, Joana; Roseira, Joana; Cancela, Eugénia; Sousa, Paula; Portela, Francisco; Correia, Luís; Moreira, Paula; Santiago, Mafalda; Dias, Sandra; Afonso, Joana; Danese, Silvio; Peyrin‐Biroulet, Laurent; Dias, Cláudia CamilaBackgroundTimely stratification of Crohn's disease (CD) is essential for patients' management. The use of noninvasive accurate biomarkers is key to monitor treatment and to pursue mucosal healing, the ultimate treatment endpoint in CD. ObjectiveWe aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression. MethodsData from 289 CD patients receiving infliximab (IFX) maintenance therapy for 2 years was collected; those patients were included in DIRECT, a prospective multicenter observational study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices. ResultsThe isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p <= 0.001] for composite outcomes 1 and 2, respectively) regardless of confounding factors. Isolated highly elevated C-reactive protein (CRP; >10.0 mg/L) and fecal calprotectin (FC; >500.0 mu g/g) in at least one visit were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 mu g/g) were only relevant when detected in at least two visits (consecutive or not). The combination of biomarkers in risk matrices had good ability to predict progression; patients simultaneously presenting anemia, highly elevated CRP and FC at least once had 42%-63% probability of achieving the composite outcomes. ConclusionThe combined evaluation of hemoglobin, CRP, and FC in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making.
- The influence of subclinical active inflammation on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patientsPublication . Magro, Fernando; Fernandes, Samuel; Patita, Marta; Arroja, Bruno; Lago, Paula; Rosa, Isadora; Sousa, Helena Tavares; Ministro, Paula; Mocanu, Irina; Vieira, Ana; Castela, Joana; Moleiro, Joana; Roseira, Joana; Cancela, Eugénia; Sousa, Paula; Portela, Francisco; Correia, Luís; Moreira, Paula; Dias, Sandra; Afonso, Joana; Danese, Silvio; Peyrin-Biroulet, Laurent; Vucicevic, Katarina M; Santiago, MafaldaBackground and aims: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study’s primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment. Methods: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model. Results: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in the majority of its definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression. Conclusion: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.
- Thiopurines have no impact on outcomes of Crohn's disease patients beyond 12 months of maintenance treatment with infliximabPublication . Sousa, Paula; Patita, Marta; Arroja, Bruno; Lago, Paula; Rosa, Isadora; Sousa, Helena Tavares; Ministro, Paula; Mocanu, Irina; Vieira, Ana; Castela, Joana; Moleiro, Joana; Cancela, Eugenia; Roseira, Joana; Portela, Francisco; Correia, Luis; Santiago, Mafalda; Dias, Sandra; Alves, Catarina; Afonso, Joana; Dias, Claudia Camila; Magro, FernandoThe emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines. Aims: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab. Methods: In this analysis of the 2 -year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C -reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug -related items was used to define treatment failure. Results: The study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub -analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021). Conclusion: In CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration.