Browsing by Author "Afonso, J."
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- Low Golimumab trough levels at week 6 are associated with poor clinical, endoscopic and histological outcomes in ulcerative colitis patients: pharmacokinetic and pharmacodynamic sub-analysis of the evolution studyPublication . Magro, F.; Lopes, S.; Silva, M.; Coelho, R.; Portela, F.; Branquinho, D.; Correia, L.; Fernandes, S.; Cravo, M.; Caldeira, Paulo; Sousa, Helena Tavares; Patita, M.; Lago, P.; Ramos, J.; Afonso, J.; Redondo, I.; Machado, P.; Cornillie, F.; Lopes, J.; Carneiro, F.Background and Aims: Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters. Methods: This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naive to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6. Results: A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 mu g/mL vs 1.3 mu g/mL, p = 0.0013; and 3.1 mu g/mL vs 1.7 mu g/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 mu g/mL vs 1.7 mu g/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]. Conclusions: A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.
- Proactive therapeutic drug monitoring of infliximab: a comparative study of a new point-of-care quantitative test with two established ELISA assaysPublication . Afonso, J.; Lopes, S.; Gonçalves, R.; Caldeira, Paulo; Lago, P.; Sousa, Helena Tavares; Ramos, J.; Gonçalves, A. R.; Ministro, P.; Rosa, I.; Vieira, A. I.; Dias, C. C.; Magro, F.BackgroundTherapeutic drug monitoring is a powerful strategy known to improve the clinical outcomes and to optimise the healthcare resources in the treatment of autoimmune diseases. Currently, most of the methods commercially available for the quantification of infliximab (IFX) are ELISA-based, with a turnaround time of approximately 8h, and delaying the target dosage adjustment to the following infusion.AimTo validate the first point-of-care IFX quantification device available in the market - the Quantum Blue Infliximab assay (Buhlmann, Schonenbuch, Switzerland) - by comparing it with two well-established methods.MethodsThe three methods were used to assay the IFX concentration of spiked samples and of the serum of 299 inflammatory bowel diseases (IBD) patients undergoing IFX therapy.ResultsThe point-of-care assay had an average IFX recovery of 92%, being the most precise among the tested methods. The Intraclass Correlation Coefficients of the point-of-care IFX assay vs. the two ELISA-based established methods were 0.889 and 0.939. Moreover, the accuracy of the point-of-care IFX compared with each of the two reference methods was 77% and 83%, and the kappa statistics revealed a substantial agreement (0.648 and 0.738).ConclusionsThe Quantum Blue IFX assay can successfully replace the commonly used ELISA-based IFX quantification kits. This point-of-care IFX assay is able to deliver the results within 15min makes it ideal for an immediate target concentration adjusted dosing. Moreover, it is a user-friendly desktop device that does not require specific laboratory facilities or highly specialised personnel.
- Serum neutrophil biomarkers to predict crohn's disease progression and infliximab treatment outcomesPublication . Magalhaes, D.; Santiago, M.; Patita, M.; Arroja, B.; Lago, P.; Rosa, I.; Sousa, Helena Tavares; Ministro, P.; Mocanu, I.; Vieira, A.; Castela, J.; Moleiro, J.; Roseira, J.; Eugenia, C.; Sousa, P.; Portela, F.; Correia, L.; Dias, S.; Afonso, J.; Danese, S.; Peyrin‐Biroulet, L.; Dias, C. C.; Magro, F.Background and aims: Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil-related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2-year period, in a real-world setting. Methods: The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study. Patients were categorized according to a composite outcome reflecting progression that included surgery, hospitalizations, new fistulae, abscess or stricture, and drug treatment escalation. Serum neutrophil elastase, lipocalin-2, lactoferrin, and resistin (non-neutrophil control) were analyzed via multiplex magnetic bead assays at multiple touchpoints. Fecal calprotectin was assessed by ELISA. Results: Over up to 2 years of follow-up, serum biomarkers did not differentiate between the composite outcome groups, whereas fecal calprotectin was significantly higher in patients with worse outcomes. During the infliximab maintenance phase, there was a significant, sustained reduction of neutrophil elastase (p < 0.001), lipocalin-2 (p < 0.001), and lactoferrin (p < 0.001), but not of resistin, despite stable neutrophil levels. Correlations between NE and NGAL levels were strong (Pearson correlations 0.75-0.85); all other correlations were of small magnitude. Conclusion: Our real-world data do not support using serum neutrophil elastase, lipocalin-2, or lactoferrin concentrations as predictors of treatment outcomes or disease evolution in infliximab -treated Crohn's Disease patients. On the other hand, the sustained decrease in biomarkers over time suggests that neutrophil stabilization might be an additional infliximab mechanism of action.
- The performance of Remicade (R)-optimized quantification assays in the assessment of Flixabi (R) levelsPublication . Magro, F.; Rocha, C.; Vieira, A. I.; Sousa, H. T.; Rosa, I; Lopes, S.; Carvalho, J.; Dias, C. C.; Afonso, J.Background: The advent of Remicade (R) biosimilars, Remsima (R), Inflectra (R) and, more recently, Flixabi (R), has brought along the potential to decrease the costs associated with this therapy, therefore increasing its access to a larger group of patients. However, and in order to assure a soft transition, one must make sure the assays and algorithms previously developed and optimized for Remicade perform equally well with its biosimilars. This study aimed to: (a) validate the utilization of Remicade-optimized therapeutic drug monitoring assays for the quantification of Flixabi; and (b) determine the existence of Remicade, Remsima and Flixabi cross-immunogenicity. Methods: Healthy donors' sera spiked with Remicade, Remsima and Flixabi were quantified using three different Remicade-quantification assays, and the reactivity of anti-Remicade and anti-Remsima sera to Remicade and to its biosimilars was assessed. Results: The results show that all tested Remicade-infliximab-optimized assays measure Flixabi as accurately as they measure Remicade and Remsima: the intraclass correlation coefficients between theoretical and measured concentrations varied from 0.920 to 0.990. Moreover, the interassay agreement values for the same compounds were high (intraclass correlation coefficients varied from 0.936 to 0.995). Finally, the anti-Remicade and anti-Remsima sera reacted to the different drugs in a similar fashion. Conclusions: The tested assays can be used to monitor Flixabi levels. Moreover, Remicade, Remsima and Flixabi were shown to have a high cross-immunogenicity, which supports their high similarity but prevents their switching in nonresponders with antidrug antibodies.