Predictive Value of Serum Infliximab Levels at Induction Phase in Rheumatoid Arthritis Patients
Teresa Jurado1, *, Chamaida Plasencia-Rodríguez2, Ana Martínez-Feito1, Victoria Navarro-Compán2, Theo Rispens3, Annick de Vries3, Karien Bloem3, Eva-María Olariaga1, Cristina Diego1, Alejandro Villalba2, Diana Peiteado2, Laura Nuño2, Maria-Gema Bonilla2, Alejandro Balsa2, Dora Pascual-Salcedo1
Identifiers and Pagination:Year: 2017
First Page: 75
Last Page: 87
Publisher Id: TORJ-11-75
Article History:Received Date: 02/01/2017
Revision Received Date: 07/03/2017
Acceptance Date: 21/04/2017
Electronic publication date: 29/06/2017
Collection year: 2017
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The Infliximab, has proven effective in treating rheumatoid arthritis (RA). A good clinical response is usually associated with high serum drug levels. Development of antibodies toward Infliximab (ATI) can increase drug clearance, leading to treatment failure.
To analyze whether serum Infliximab trough levels (ITL) at the induction phase are associated with Infliximab clearance and clinical outcomes at week(W) 54 and to investigate the association with immunogenicity development.
Observational retrospective study in which ITL from 66 RA patients were measured by capture ELISA at W0, W2, W6, W14 and 22. Patients were classified as ITLpos if Infliximab was detectable at W54 and ITLneg otherwise. ATI were assayed by bridging ELISA and by two drug-tolerant assays. ITL cut-off values were established by ROC curves. The association between ITL at early-stage and clearance of Infliximab at W54 was analyzed by univariable and multivariable logistic regression.
ITLneg patients (n=25) always had significantly lower Infliximab levels than ITLpos (n=41). An ITL value of 4.4 μg/mL at W6 best predicted W54 Infliximab absence. In the multivariable analysis, only ITL below the cut-off at W6 (OR: 86.6; 95%CI: 6.58-1139.99) and non-use of methotrexate (OR: 6.9; 95%CI: 1.04-45.84) remained significantly associated with W54 Infliximab absence. ATI were more frequent in patients with ITL below the cut-off at W6.
In RA, ITL at induction phase are inversely associated with Infliximab clearance and clinical outcomes at W54. ATI was the main reason for low early ITL. A predictive value of ITL at W6 was found as a useful prognostic measure of treatment efficacy.