P545 The effect of total and free anti-drug antibodies on infliximab pharmacokinetics between 2 drug administrations
L. Roque Ramos1, R. Barosa1, A. Nunes2, A. Regalado3, A. Vieira1, J. Freitas1, J. Demengeot3, S. Garcês*4
1Hospital Garcia de Orta, Gastroenterology, Almada, Portugal, 2Hospital Garcia de Orta, Department of Gastroenterology, Almada, Portugal, 3Instituto Gulbenkian Ciência, Oeiras, Portugal, 4Hospital Garcia de Orta, Rheumatology, Almada, Portugal
When performed, the monitoring of ADA is generally restricted to the detection of free ADA (fADA) at trough, that is, those that are not in complex with the drug. fADA may underestimate the prevalence of ADA-positive patients. New assays, based on immunocomplexes dissociation, are available for detection of total ADA (tADA), free and in complex. However, the clinical relevance of measuring tADA remains unclear.
We evaluated the effect of fADA and tADA on infliximab’s pharmacokinetic, over the interval between 2 drug administrations, in a cohort of adult IBD (inflammatory bowel disease) patients under maintenance therapy. Infliximab (IFX) levels, fADA and tADA titres were measured, using an ELISA (enzyme-linked immunosorbent assay) assay, on a weekly schedule, between 2 IFX administrations and correlated to clinical outcomes.
We included 22 IBD patients (17 Crohn’s disease and 5 ulcerative colitis), receiving the standard IFX dose (n = 18) or an intensified regimen (n = 4), for a median (IQR) duration of 3.4 (0.8–4.6) years. At trough, 64% and 36% of patients tested positive for tADA and fADA, respectively. tADA titres remained stable over the entire therapeutic interval. Patients were empirically stratified in 3 groups according to tADA levels: low (≤ 20 AU/mL), moderate (20–80 AU/mL), and high (≥ 80 AU/mL). All fADA positives had moderate to high tADA titres. In the low-tADA group, 38% were also fADA positives, although at a very low titre. Trough levels of IFX > 1ug/mL were observed in all tADA-negatives and in 50% of low tADAb patients by the end of the interval. In contrast, patients with high tADAb had undetectable IFX levels by the second to third weeks after the infusion. Clinical and biological remission was observed in all patients without tADA, and in 63% of the tADA low. Infusion reactions occurred in all tADA positive groups but not in the tADA negative patients.
tADA measurement is reliable to assess immunogenicity, and contrarily to fADA is informative at any time point between 2 administrations. Patients with moderate-high tADA titres also tested positive for fADA, but the majority of low-tADA were fADA negatives. High tADA titres rapidly reduce drug bioavailability, whilst low-tADA titres have little effect on drug’s pharmacokinetics, although they may reveal patients at risk to develop clinically relevant immunogenicity.