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
1 Immunology Unit, University Hospital La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
2 Rheumatology Department and Institute for Health Research (IdiPAZ), University Hospital La Paz, Madrid, Spain.
3 Sanquin Research; Department Immunophatology; Amsterdam, The Netherland; and Landsteiner Laboratory; Academic Medical Centre; University of Amsterdam; Amsterdam, The Netherlands.
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.
Keywords: Infliximab therapy, Rheumatoid Arthritis, Induction phase, Levels clearance, Loss of efficacy, Early immunogenicity.
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* Address correspondence to this author at the Immunology Unit, University Hospital La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain; Tel: (+34) 91 2071060; Fax: (+34) 91 7277095; E-mail: email@example.com