Serum Levels of Infliximab and Anti-Infliximab Antibodies in Brazilian Patients with Crohn's Disease

Abstract

OBJECTIVES: The aim of this study was to evaluate the quantitative serum level of infliximab (IFX) as well as the detection of anti-infliximab antibodies (ATIs) in patients with Crohn's disease (CD). METHOD: Forty patients with CD under treatment at a tertiary center in southeastern Brazil were evaluated. Their use of infliximab was continuous and regular. We analyzed and compared the differences in the IFX and ATI levels between the patients with active CD (CDA) and those with CD in remission (CDR). RESULTS: There was no difference in the IFX level between the CDA and CDR groups ( p >0.05). Eighty percent of all patients had IFX levels above the therapeutic concentration (6-10 μg/mL). Two (9%) of the 22 patients with active disease and four (22.2%) of the 18 patients in remission had undetectable levels of IFX. Four (66.6%) of the six patients with undetectable levels of IFX had positive ATI levels; three of these patients were in remission, and one had active disease. In addition, the other two patients with undetectable levels of IFX presented ATI levels close to positivity (2.7 and 2.8 AU/ml). None of the patients with therapeutic or supratherapeutic IFX levels had positive ATI levels. CONCLUSIONS: The undetectable levels of IFX correlated with the detection of ATIs, which was independent of disease activity. Immunogenicity was not the main factor for the loss of response to IFX in our study, and the majority of patients in both groups (CDA and CDR) had supratherapeutic levels of IFX.

Post-Induction High Adalimumab Drug Levels Predict Biological Remission at Week 24 in Patients With Crohn's Disease

“…Our results, using a prospective approach and with assessment of biological endpoints, provide information that is not evident from clinical data alone. Our finding of a lack of association of ADL trough levels with clinical remission is consistent with the recently reported findings of a Brazilian study, albeit on IFX in CD ( 31 ). In that study, drug trough levels did not differ between individuals with active CD and those with CD in remission.…”

Authors' Reply – Comments: Serum levels of infliximab in Brazilian patients with Crohn's disease: what are the reasons for differences from previous studies?

“…Concerning the similar anti-TNFα levels that we observed in both the active disease and remission groups 2, other studies in the literature have already noted this phenomenon 16,17. Patients with active mucosal disease may present a higher rate of serum-to-tissue drug level mismatch compared to those in remission 17.…”

“…We would like to thank Teixeira et al 1 for their comments on our article 2. They correctly noted that the majority of our patients presented infliximab (IFX) levels above the therapeutic concentration, differing from three other Brazilian studies published between 2017 and 2018 3-5.…”

“…Concerning the comments of Teixeira et al 1 about why we might have mixed the results of the study because several patients with levels between 3-6 µg/mL would be considered adequate according to the range of 3-7 µg/mL but infratherapeutic according to our adopted range (6-10 µg/mL), we would like to clarify that, as described in our manuscript 2, there were no patients with levels between 3-6 µg/mL. Of the few patients we had with IFX trough levels ≤ 5 µg/mL, all presented undetectable levels (<0.035 µg/mL), and they correlated 100% with positive ATIs, demonstrating the accuracy of the test.…”

Serum levels of infliximab in Brazilian patients with Crohn's disease: what are the reasons for differences from previous studies?

“…It was with significant interest that we read the manuscript, entitled“Serum Levels of Infliximab and Anti-Infliximab Antibodies in Brazilian Patients with Crohn's Disease”, recently published in this distinguished journal by Gomes et al (1). In this study, the authors measured the serum infliximab (IFX) levels of 40 patients with Crohn's disease (CD) and correlated their findings with disease activity.…”