Sirs, In an interesting article, Ben-Horin et al. report that anti-infliximab (IFX) antibodies (Ab) are detectable in only a small minority of IBD patients at 1 year after discontinuation of IFX (3 of 16 patients, 19%). We have recently monitored the decline of anti-IFX Ab in 56 IBD patients and found that 77%, 62%, 36%, 25% and 0%, respectively, had detectable anti-IFX Ab when tested 0–1, 1–2, 2–3, 3–4 and >4 years after discontinuation of IFX.
There may be several explanations for these discrepancies, including the larger sample size of our study, a different composition of patients with Crohn's disease and ulcerative colitis (Ben-Horin included nine and seven, we included 46 and 10), and the extent of repeated anti-IFX Ab measurements in individual patients.
The use of different assays may also add to the conflicting findings. While our radioimmunoassay (RIA) uses anti-human λ Ab for detection, as in the capture ELISA used by Ben-Horin et al., binding in RIA takes place in fluid-phase and without addition of TNF-α. This RIA has been extensively clinically validated in IBD and other diseases.[3-6] It has a higher sensitivity for anti-IFX Ab detection than bridging and capture ELISAs, and is capable of detecting all subtypes of anti-IFX Ab including monovalent IgG4 Ab, which predominate during long-term immunisations.
This subclass of Ab, although detectable in capture ELISA, are not detected in bridging ELISAs. Solid-phase assays may also give false negative results due to epitope masking. Finally, anti-idiotypic Ab may go unnoticed in ELISAs where the capture phase consists of IFX bound to high-level TNF-α-coated plastic (Figure 1), a problem also noted by Ben-Horin et al.
Our conclusion is that anti-IFX Ab can persist for years after discontinuing the drug. The impact on efficacy and safety of pre-existing anti-IFX Ab prior to IFX retreatment remains to be definitively established.