Introduction Anti-TNF antibody, infliximab (IFX), is highly effective in inducing and maintaining remission of patients with Inflammatory Bowel Diseases (IBD). However, a large portion of patients develop secondary loss of response mainly due to the formation of antibodies to infliximab (ATI). The strong correlation between IFX levels, ATI and loss of clinical response is widely acknowledged. In order to improve existing algorithms for the management of patients with therapeutic drug monitoring data, drug cut-offs must be implemented. The aim of the present study was to determine therapeutic cut-off level of IFX in patients with IBD categorised as in remission or with active disease.
Method A total of 50 patients were retrospectively included (33 patients with Crohn´s disease and 17 with ulcerative colitis). Patients were routinely assessed by endoscopic evaluation. Serum was collected immediately before the infusion (trough levels) and stored until the analysis. IFX and ATI trough levels were measured with Promonitor-IFX and Promonitor-ANTI-IFX ELISA kits (Progenika, Spain). Measurement range allowed quantification across the clinically relevant range of 0.035 to 14.4 µg/mL for IFX and 5 to 1440 AU/mL for ATI. Forty three (86%) and seven (14%) patients were categorised as in remission and active disease, respectively.
Results IFX trough levels were significantly higher in patients classified as in remission (median 3.1 µg/mL, IQR 1.5–5.1, n = 43) compared to those who had active disease (median 0 µg/mL, IQR 0–0.5, n = 7; p < 0.001). Using receiver operating characteristics (ROC) analysis an optimal IFX cut-off value of <0.8 µg/mL was determined. An area under the curve of 0.86 (95% CI 76–96) was determined. This cut-off establishes the IFX level below which the drug level is associated with active disease with a sensitivity of 86% (95% CI 42–99) and specificity of 75% (95% CI 62–85; p = 0.002). Four patients (57%) with active disease showed ATI as compared to only 7% of patients classified as in remission (p < 0.001). All patients with ATI showed no IFX levels. One patient with active disease showed an infusion-related reaction (459 AU/mL of ATI). Results are in agreement with previously published studies confirming the IFX cut-off.
Conclusion ELISA is a simple and powerful technology that provides an accurate quantitation of IFX levels and excellent correlation with clinical outcome. The measurement of IFX and ATI trough levels can help to make a more rational management of patients with IBD. The cut-off level of IFX described in this study can be easily used to discriminate between different clinical responses and guide IFX therapy.
Disclosure of interest D. Nagore Employee of: Progenika, A. Ruiz del Agua Employee of: Progenika, J. Pascual Employee of: Progenika, F. Llinares-Tello: None Declared, B. Herreros: None Declared, A. Martínez Employee of: Progenika, S. Martín Grant/ Research Support from: Progenika, R. Navarro: None Declared.