Background/Purpose: Treatment of RA with biologic TNF inhibitors is effective in reducing disease activity and improving radiographic progression outcomes. Therapeutic drug monitoring (TDM) of adalimumab (ADL) concentration and anti-adalimumab antibody titers may be used to expedite medication decisions, optimize dosing to improve efficacy, and may lead to reduced biologic waste. ADL drug and anti-ADL antibody (ADA) assays have been validated and used in published studies in peer-reviewed literature. Recently approved by the FDA, adalimumab-atto is a biosimilar of the originator adalimumab (TNF-α inhibitor). Here, we quantitate serum levels of the biosimilar drug and its ADA levels and show equivalency of these assays to those for the originator drug.

Methods: Adalimumab-atto -specific immunoassays for drug and anti-drug antibody were developed. Adalimumab-atto calibrators and adalimumab-atto conjugated key reagents were used. Analytical performance including spike and recovery, specificity and selectivity was assessed. Exogenous adalimumab-atto was spiked into donor serum in the presence or absence of ADL to assess recovery using the originator ADL drug assay. Forty ADL-treated patients were split-tested using both adalimumab-atto and originator drug and ADA assays to assess equivalency and transferability between the two methods. Results were statistically analyzed and compared.

Results: Both adalimumab-atto drug and ADA assays showed excellent agreement to originator ADL drug and anti-drug assays. Significantly, spike and recovery of adalimumab-atto using the ADL drug assay was equivalent to the recovery of originator ADL using the ADL drug assay. Adalimumab-atto 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 originator ADL. Both sets of targets were read using the ADL drug assay. Percent recovery of adalimumab-atto ranged from 87% to 117%; ADL recovery was 95% to 108%. Both the adalimumab-atto drug assay and ADL drug assay was used to analyze 40 clinical serum samples treated with originator ADL. The calculated linear regression between the two methods was Y=0.967x-0.64 and r²=1.0. The adalimumab-atto-specific ADA assay performed equivalently to the originator ADL ADA assay in terms of method comparison. Forty anti-ADL antibody positive clinical serum samples were tested using the adalimumab-atto ADA assay and antibody titer values were compared, producing a linear regression of Y=0.989x+35.8, r² = 1.0.

Conclusion: This study demonstrates complete cross-reactivity of biosimilar adalimumab-atto and originator adalimumab using the originator ADL drug and anti-drug antibody assays.  Analytical performance of all tested parameters demonstrated equivalency. Therefore, clinicians can confidently use the originator ADL tests to monitor drug levels and ADA titers in patients on the biosimilar adalimumab-atto.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/therapeutic-drug-monitoring-of-the-adalimumab-biosimilar-amjevita-adalimumab-atto-using-originator-adalimumab-and-anti-adalimumab-antibody-assays/