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 study
| العنوان: | 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 study |
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| المؤلفون: | Paulo Caldeira, F Cornillie, P Machado, Marília Cravo, Susana Lopes, Fátima Carneiro, Helena Sousa, I Redondo, Rosa Coelho, Joanne Lopes, Luis M. Correia, Fernando Magro, Jaime A. Ramos, Paula Lago, Diogo Branquinho, Francisco Portela, Marta Patita, S. Fernandes, Joana Afonso, M. Silva |
| المصدر: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| بيانات النشر: | Oxford University Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, medicine.medical_specialty, Induction Phase, Gastroenterology, Golimumab, Drug Administration Schedule, Endoscopy, Gastrointestinal, Induction, Trough levels, Feces, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, Pharmacokinetics, Internal medicine, medicine, Humans, In patient, Disease, Prospective Studies, Glucocorticoids, Dose-Response Relationship, Drug, Portugal, business.industry, Remission Induction, Antibodies, Monoclonal, General Medicine, medicine.disease, Ulcerative colitis, Faecal calprotectin, C-Reactive Protein, 030104 developmental biology, Pharmacodynamics, Biomarker (medicine), Colitis, Ulcerative, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Therapy, business, Leukocyte L1 Antigen Complex, Biomarkers, Immunosuppressive Agents, medicine.drug |
| الوصف: | 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 naïve 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 μg/mL vs 1.3 μg/mL, p = 0.0013; and 3.1 μg/mL vs 1.7 μg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 μg/mL vs 1.7 μg/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. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::519d54e75c6a5c995df44fc4891c8e0b |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....519d54e75c6a5c995df44fc4891c8e0b |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |