Comparison of a new rapid method for the determination of adalimumab serum levels with two established ELISA kits

Abstract

Background Therapeutic drug monitoring (TDM) of adalimumab (ADA) in inflammatory bowel diseases (IBDs) has gained increased attention since several studies showed a correlation between drug levels and mucosal healing. The limitations of routine usage of enzyme-linked immunoabsorbent assay (ELISA) kits for measuring serum ADA concentrations have prompted the development of rapid methods, such as Quantum Blue (QB). We evaluated the interchangeability and agreement between the QB method and two established ELISA kits, Promonitor (PM) and Lisa-Tracker (LT). Methods Fifty samples from patients with IBD were included. Quantitative analysis was performed using the ANOVA test for repeated measures, Deming regression and the Bland-Altman plot. Clinical implications were evaluated by concordance in classifying patients into therapeutic windows according to the proposed cut-off levels for subtherapeutic (either <5 or <7.5 μg/mL) and supratherapeutic (>12 μg/mL) ranges. Results Statistical differences were detected between the QB method and the two ELISA kits, with QB overestimating ADA serum values compared to them. A lack of interchangeability was observed between methods, with greater differences as ADA levels increased. An analysis of a sub-set of samples with ADA values below 9 μg/mL (n = 25) showed that QB fulfilled the criteria to be interchangeable with the LT assay. Concordance for patient classification into ADA therapeutic windows was better for QB vs. LT than for QB vs. PM, with high agreement (>75%) for subtherapeutic levels among the three methods. Conclusions Although quantitative differences existed between the rapid method and ELISA kits that hampered their interchangeability, the agreement for identifying patients with subtherapeutic values of ADA was high.

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

“…In studies where these ELISA formats were compared, a good correlation between them was shown (correlation coefficients >0.9). 26 27 29 40 41 Other assay formats also correlated well with ELISA. In four studies, ELISA was compared with homogenous mobility shift assay (HMSA).…”

“…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.…”

“…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. There are two types of ELISAs available: direct ELISA, characterised by non-specific detection of the analyte, and sandwich ELISA, characterised by specific detection of the analyte.…”

The First WHO International Standard for Adalimumab: Dual Role in Bioactivity and Therapeutic Drug Monitoring

“…In the infliximab case, despite an excellent correlation of infliximab levels between assays, a substantial variation in some results and systematic biases of infliximab trough levels was noted which could result in divergent therapeutic decisions for some patients (83). Similarly, in the comparative study measuring adalimumab levels in patient sera, a lack of interchangeability between methods was observed, with greater differences noted as ADA levels increased (84). This disagreement in results, evident also in other studies, has led to calls from several groups for the need for standardization of assays for detection of levels of anti-TNFs and ADA in clinical samples (32,33,73).…”

Advances in Therapeutic Drug Monitoring in Biologic Therapies for Pediatric Inflammatory Bowel Disease

“…Point-of-care assays for detecting IFX levels, adalimumab levels, and anti-IFX antibodies are commercially available. However, they are limited by their ability to use serum instead of blood (58)(59)(60). As with other point-of-care tests, there are concerns around quality control, reliability, cost, and external validation.…”