The Kinetics of Anti-Drug Antibodies, Drug Levels, and Clinical Outcomes in Infliximab-Exposed Patients with Immuno-Mediated Disorders

Publication date: Available online 13 April 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Nencini Francesca, Vultaggio Alessandra, Pratesi Sara, Cammelli Daniele, Milla Monica, Fiori Ginevra, Bagnoli Siro, Prignano Francesca, Romagnani Sergio, Maggi Enrico, Matucci Andrea
BackgroundHypersensitivity reactions (HRs) and loss of response (LOR) to infliximab (IFX) are related to drug immunogenicity characterized by anti-drug antibodies (ADA).ObjectiveTo analyse the timing of ADA appearance, and its relationship with drug levels and clinical outcomes in IFX-treated patients with different diseases.MethodsSamples were longitudinally collected before each infusion from 91 IFX-treated patients and were assayed for ADA and drug levels by ELISA and for IgE by CAP-system Clinical data were also monitored, regarding efficacy and safety of therapy.ResultsThe ADA onset occured quite early, irrespective of the type of disease, during the first year and more frequently andearlier during the second cycle of therapy. HR patients were more frequently ADA+ and with higher ADA titers compared to other patient groups. ADA onset tends to precede HRs and LOR; all HRs that occur after a period of drug interruption are preceded by ADA development. Before ADA detection, a progressive decline of IFX levels until a complete disappearance was observed. The ADA titre was maintained for years both in patients with ongoing therapy and in those who interrupted it. IgE ADA are more frequently developed in patients with higher and earlier ADA levels, but their rate of negativization is faster.ConclusionsThe present data suggest that most IFX-exposed patients develop ADA within the first year of treatment irrespective of disease type. The clinical outcome to the treatment is preceded by ADA development, which in turn, is aassociated with the reduction of drug serum levels. Both ADA evaluation, as well as therapeutic drug monitoring, may have a relevant impact on clinical practice, giving new insights to predict LOR and HR.