Serum Infliximab Measurement in Inflammatory Bowel Disease Patients in Remission: A Comparative Analysis of Two Different Methods in a Multicentric Brazilian Cohort

Abstract

BACKGROUND: Infliximab (IFX) therapeutic drug monitoring is an important tool to guide therapeutic decision in inflammatory bowel disease patients. Currently, there are two methods to measure trough levels of IFX, ELISA assays or rapid tests. Despite that the ELISA assay is the most used method in therapeutic drug monitoring, the results take long to be available for clinical use, and it needs to be performed by trained personnel. In contrary, the results of a rapid test take 20 to 30 minutes to be available and can be performed by non-trained lab personnel. OBJECTIVE: The aim of the study was to compare a rapid test (QB-IFX) for quantitative determination of IFX level to one ELISA assay in a cohort of inflammatory bowel disease patients. METHODS: Cross-sectional multicentric study with 49 inflammatory bowel disease patients on maintenance therapy with IFX. Blood samples for IFX serum levels were collected immediately before infusion. IFX serum levels were classified as undetectable, low (<3.0 μg/mL), adequate (3.1-7.0 μg/mL) or high (>7.1 μg/mL). A sensitivity and specificity of each test and a comparison between tests was based on ROC curves. RESULTS: Thirty-four Crohn’s disease patients and 15 ulcerative colitis patients in clinical remission were evaluated. The majority of patients had low or adequate serum levels of IFX. In relation to the serum levels proportions with the two methods, there was no significant difference (P=0.84). The ROC analysis identified a concentration threshold >2.9 μg/mL with the QB-IFX test (area under the ROC, 0.82; P<0.0001, sensitivity, 100%; specificity, 61.9%), and >3.83 μg/mL using the ELISA assay (area under the ROC, 0.96; P<0.0001, sensitivity, 100%; specificity, 92.9%). CONCLUSION: QB-IFX and ELISA assays to measure IFX levels were comparable. Both methods had accurate sensitivity and specificity to detect undetectable, low and adequate levels, but had showed low specificity for supra therapeutic levels of IFX.

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

“…Similar supra-therapeutic levels were found by Parra et al (11.3%) in a study using the Quantum Blue rapid test (5). In another multicentric study, similar proportions were also found (8.16% with a different ELISA assay and 16.33% with the Quantum Blue rapid test) (6). The percentage of supra-therapeutic levels found by Gomes et al (80% of the sample), even considering the upper limit of 10 µg/mL, is extremely high and not compatible with other studies from the same country.…”

Therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal disease: a systematic literature review informing EULAR points to consider

“…Regarding point-of-care tests, two types were widely studied, namely, Quantum Blue and lateral flow assay. Both showed a good correlation with ELISA in seven observational studies 27 28 30 31 35 39 41. In one study, both point-of-care methods are compared with each other and demonstrate good correlation 41…”

“…Several assay formats are available to measure biopharmaceutical blood concentrations, of which ELISA is the most widely used. In total, 20 studies were identified that compared two or more formats for biopharmaceutical blood concentration measurement 23–42. In 12 studies, agreement between different assay formats and ELISA formats was investigated 23–27 29 34 36 37 40–42.…”

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

“…However, Kampa et al themselves admitted that the limitations of their paper were its retrospective character (failures in data collection might occur) and the absence of a detailed description of the clinical and endoscopic conditions at the moment of collection. Additionally, the aim of Teixeira et al 4 was to measure the serum levels of IFX by comparing two different, already validated, assays 6,7. Although this approach was indeed interesting, the majority of patients included in the study (88%) were in remission, a condition that is not impacted by therapeutic drug monitoring in clinical practice.…”

“…Although this approach was indeed interesting, the majority of patients included in the study (88%) were in remission, a condition that is not impacted by therapeutic drug monitoring in clinical practice. Teixeira et al 4 even suggested that more studies on patients with active disease would be necessary. Finally, Parra et al 5 evaluated the levels of IFX in a larger cohort of 55 patients with CD and 16 with UC.…”