F Magro1,2, S Lopes1, M Silva1, R Coelho1, F Portela3, D Branquinho3, L Correia4, S Fernandes4, M Cravo5, P Caldeira6, H T Sousa6, M Patita7, P Lago8, J Ramos9, J Afonso2, I Redondo10, P Machado10, F Cornillie11, J Lopes2, F Carneiro2,12. 1. Centro Hospitalar São João, Departamento de Gastrenterologia, Porto, Portugal. 2. Faculdade de Medicina, Universidade do Porto, Porto, Portugal. 3. Centro Hospitalar Universitário de Coimbra, Departamento de Gastrenterologia, Coimbra, Portugal. 4. Centro Hospitalar Lisboa Norte, Departamento de Gastrenterologia, Lisboa, Portugal. 5. Hospital Beatriz Ângelo, Departamento de Gastrenterologia, Loures, Portugal. 6. Centro Hospitalar Universitário do Algarve, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, Algarve Biomedical Centre, Universidade do Algarve, Faro, Portugal. 7. Hospital Garcia de Orta, Departamento de Gastrenterologia, Almada, Portugal. 8. Centro Hospitalar do Porto, Departamento de Gastrenterologia, Porto, Portugal. 9. Centro Hospitalar Lisboa Central, Departamento de Gastrenterologia, Lisboa, Portugal. 10. MSD Portugal, Medical Affairs, Paço de Arcos, Portugal. 11. Merck Sharp & Dohme, Kriens, Switzerland. 12. Instituto de Patologia e Imunologia Molecular da Universidade do Porto [Ipatimup], i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Abstract
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.
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.
Authors: Fernando Magro; Susana Lopes; Marco Silva; Rosa Coelho; Francisco Portela; Diogo Branquinho; Luís Correia; Samuel Fernandes; Marília Cravo; Paulo Caldeira; Helena Tavares de Sousa; Marta Patita; Paula Lago; Jaime Ramos; Joana Afonso; Isabel Redondo; Patrícia Machado; George Philip; Joanne Lopes; Fátima Carneiro Journal: Therap Adv Gastroenterol Date: 2019-08-30 Impact factor: 4.409
Authors: Jan Marsal; Manuel Barreiro-de Acosta; Irina Blumenstein; Maria Cappello; Thomas Bazin; Shaji Sebastian Journal: Front Med (Lausanne) Date: 2022-06-15