title: Monitoring of adalimumab and antibodies-to-adalimumab levels in patient serum by the homogeneous mobility shift assay.
abstract: This report describes the analytical validation and application of the homogeneous mobility shift assay (HMSA) method for the measurement of adalimumab and human antibodies-to-adalimumab (ATA) in serum samples from patients who have lost response to adalimumab treatment. Validation of the ATA- and the adalimumab-HMSA revealed a lower limit of detection to be 0.026 U/mL for ATA and 0.018 μg/mL for adalimumab in serum samples. Intra-assay and inter-assay precision determination yielded a coefficient of variation of less than 15%, and the accuracy of both assays was within 20%. Adalimumab drug tolerance in the ATA-HMSA was up to 20 μg/mL in the test serum. Serum samples from 100 drug-naïve healthy subjects were tested to set-up the cut point of 0.55 U/mL for ATA and 0.68 μg/mL for adalimumab. Analysis of 100 serum samples from patients who were losing response to adalimumab showed that 26% had an adalimumab level below the cut point, of these 68% were ATA positive. Overall, 44% of the patients (44/100) were positive for ATA. This study presents evidence that drug and anti-drug antibody levels are important determinants of patient response to therapy.
authors: Department of Research and Development, Prometheus Laboratories, Inc., 9410 Carroll Park Drive, San Diego, CA 92121, USA.
authors: Shui-Long
authors: SL
authors: Wang
authors: Scott
authors: S
authors: Hauenstein
authors: Linda
authors: L
authors: Ohrmund
authors: Reshma
authors: R
authors: Shringarpure
authors: Jared
authors: J
authors: Salbato
authors: Rukmini
authors: R
authors: Reddy
authors: Kevin
authors: K
authors: McCowen
authors: Shawn
authors: S
authors: Shah
authors: Steven
authors: S
authors: Lockton
authors: Emil
authors: E
authors: Chuang
authors: Sharat
authors: S
authors: Singh
mesh_terms: D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood* / Q000276:immunology; D002138:Calibration; D006801:Humans; D057230:Limit of Detection; D015203:Reproducibility of Results
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D000068879:Adalimumab