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 Escalation

• Autor(a) principal: Magro, Fernando
• Data de Publicação: 2017
• Outros Autores: 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, Fátima
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/11430
• topic: Inflammatory-bowel-disease; Fecal Calprotectin; Maintenance therapy; Crohns-disease; Metaanalysis; Outcomes; Marker; Assays; Index

Although 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.