Therapeutic Drug Monitoring of the Biosimilar (AMJEVITA™, Adalimumab-atto) Using Labcorp Adalimumab Assay for Drug Level and Anti-Drug Antibodies
Background:
Therapeutic drug monitoring (TDM) of adalimumab (ADL) concentration and anti-adalimumab antibody titers informs physician clinical decision-making in the management of inflammatory bowel disease (IBD). A TDM-based approach has shown to improve clinical efficacy and longevity of anti-TNF therapies. LabCorp ADL TDM assays (drug and anti-drug antibody (ADA) levels) has been validated and published in peer-reviewed literature and is widely used by clinicians to help maximize treatment response. Recently approved by the FDA for treatment of IBD, Amjevita™ (adalimumab-atto) is a biosimilar of the originator adalimumab (TNF-α inhibitor). The aim of this study was to validate the LabCorp ADL TDM test for the quantification of serum Amjevita™ concentrations and ADA.
Methods:
To demonstrate ability to measure Amjevita using the LabCorp ADL TDM test, Amjevita-specific immunoassays for drug and anti-drug antibody were developed. Amjevita calibrators and Amjevita-conjugated key reagents were used for this Amjevita method. Analytical performance including accuracy, precision, spike and recovery, specificity and selectivity was assessed. Exogenous Amjevita was spiked into donor serum to assess recovery using the ADL drug assay. Forty ADL-treated IBD patients were split-tested using Amjevita and ADL drug and anti-drug assays to assess equivalency and transferability between the two methods. Results were statistically analyzed and compared.
Results:
Both Amjevita drug and anti-drug assays showed excellent agreement to ADL drug and anti-drug assays respectively. Amjevita assay accuracy (< 12% bias) and precision (< 6.5% CV) were equivalent to ADL accuracy (< 10% bias) and precision (< 4.6% CV) across the measuring range of the assay. More importantly, spike and recovery of Amjevita using the ADL drug assay was equivalent to the recovery of reference product ADL using the ADL drug assay. Amjevita was spiked into the donor serum pool to generate 0.1, 0.5, 2.5, 10, 20, 40 and 80 ug/mL targets. The same target concentrations were generated for ADL. Both sets of targets were read using the ADL drug assay. Percent recovery of Amjevita ranged from 87% to 114%; ADL recovery was 83% to 113%. Average spike and recovery were 99% for both Amjevita and ADL using the ADL drug assay. Both the Amjevita drug assay and ADL drug assay was used to analyze 40 serum samples of IBD patients treated with reference product ADL. The calculated linear regression between the two methods was Y=0.967x-0.64 and r2=1.00. The Amjevita-specific anti-drug antibody assay performed essentially identically to the reference product ADL anti-drug assay in terms of precision (< 11.5 % CV), accuracy (< 7.9% bias), linearity, drug tolerance and sensitivity. Forty anti-ADL antibody positive serum samples from IBD patients were tested using the Amjevita anti-drug antibody assay and antibody titer values were compared. Linear regressions of Y=0.989x+35.7, r2 = 1.00 were obtained.
Conclusions:
This study demonstrates complete cross-reactivity of Amjevita vs. originator adalimumab using the LabCorp ADL TDM assays. Analytical performance of all tested parameters demonstrated equivalency. Healthcare providers can confidently use the LabCorp ADL TDM test to monitor Amjevita serum drug levels and ADA titers in their patients.
