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

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 multice...

Full description

Bibliographic Details
Main Authors: Fernando Magro, Joana Afonso, Susana Lopes, Rosa Coelho, Raquel Gonçalves, Paulo Caldeira, Paula Lago, Helena Tavares de Sousa, Jaime Ramos, Ana Rita Gonçalves, Paula Ministro, Isadora Rosa, Ana Isabel Vieira, Patrícia Andrade, João-Bruno Soares, Diana Carvalho, Paula Sousa, Tânia Meira, Joanne Lopes, Joana Moleiro, Cláudia Camila Dias, Amílcar Falcão, Karel Geboes, Fatima Carneiro
Format: Article
Language:English
Published: Elsevier 2017-07-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396417302323
Description
Summary: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 μg/mL vs. 1.15 μg/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 μg/mL (HR = 0.119, p = 0.010), and increased for patients with fecal calprotectin (FC) level above 250 μg/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.
ISSN:2352-3964