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Anti-Infliximab antibodies and drug levels: kinetics and clinical outcomes

Published online: April 13, 2018

Infliximab (IFX) is immunogenic and its administration may elicit a sensitization characterized by the development of anti-drug antibodies (ADA).  ADA seriously complicate IFX therapy since they affect the efficacy and the safety of the treatment, leading to loss of response (LOR) and hypersensitivity reactions (HRs). In previous studies it has been shown that ADA levels inversely correlate with drug levels and therapeutic response. However, the timing of ADA appearance, and its relationship with drug levels and clinical outcomes in IFX-treated patients with different diseases has not been extensively investigated.
In a recent article published in The Journal of Allergy and Clinical Immunology: In Practice, Nencini and colleagues examined the kinetics of ADA development and of IFX serum levels in treated patients, monitoring the clinical outcome to the treatment. Serum samples were longitudinally (even for many years) collected before each infusion from 91 IFX-treated patients suffering from different immune-mediated diseases, and were assayed for ADA and drug levels by ELISA and for IgE by CAP-system. Clinical data were also monitored regarding the efficacy and safety of therapy.

The authors found that ADA onset occured quite early during the first year, irrespective of the type of disease.  Patients with HRs were more frequently ADA+ and with higher ADA titers compared  to other patient groups. ADA onset tends to preceed HRs and LOR. Before ADA detection, a progressive decline of IFX levels until a complete disappearance was observed. ADA developed more frequently and earlier during the second cycle of therapy; all HRs that occured after a period of drug interruption were preceded  by ADA development. The ADA titre was maintained for years, both in patients with ongoing therapy and in those who interrupted it. IgE ADA more frequently developed in patients with higher and earlier ADA levels.

The 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 preceded by 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 into predicting LOR and HR.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.