Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: The development of the biological DMARDs has benefitted patients, who previously had no treatment options. Currently no method for stratifying patients to these drugs exist. The biochemistry profile of the patients varies (Meyer et. al. 2016), suggesting that patients need an individualized biochemistry evaluation to improve the stratification process. This is, however, a long term and challenging goal, that will possibly reduce the overall cost of treatment and reduce side effects. Meanwhile, patients in current treatment could benefit today by optimizing their current treatment, through drug concentrations measurements in addition to immune response evaluation. This can be done my immunoassays, but these are not readily scalable, thus we apply targeted proteomics. This requires sequence information of the biological drug, which might not be available. Thus, we present strategies for de-novo sequencing prior to analysis, and show that this proteomics approach readily transfers between biosimilar drugs. The aim of this study was to develop generic scalable and multiplexed targeted mass spectrometry assays to measure four selected biological drugs abatacept, tocilizumab, infiliximab, and biosimilar infliximab in patient sera for therapeutic drug monitoring in RA patients.
30 patients with rheumatoid arthritis in stable i.v. treatment with the four selected biological drugs, are being enrolled in this study and sampled before and after administration of drug. Tandem mass spectrometry, i.e. MALDI-TOF lift-mode, and LC-MS/MS on pure biological drug samples were used to de-novo sequence peptides, build spectral libraries, and subsequently utilized for patient analysis. A parallel-reaction monitoring (PRM) LC-MS/MS assay was developed and applied to targeted peptides unique to the biological drugs.
Peptides were readily sequenced using MALDI-TOF, and the resulting data, i.e. unique peptide sequences of the four biologics, molecular mass, charge, and chromatographic retention time were used for quantitative targeted PRM on patient samples.
Using the exact preparation and analysis method on infliximab, and biosimilar infliximab provides the same result, due to the shared peptide sequence (Figure 1). This indicates that future biosimilar drugs can be readily quantified with targeted proteomics with no method modifications.
Our targeted strategy highlights the strength of proteomics, and targeted proteomics for therapeutic drug monitoring in RA patients. This data-driven strategy will be important in personalized rheumatic medicine by enabling treat-to-concentration therapy.
To cite this abstract in AMA style:Meyer MK, Andersen M, Stausbo TV, Bennike TB, Andersen GN, Stensballe A. Strategies for Biological Drug Quantification in Biological Drug Immune Responses [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/strategies-for-biological-drug-quantification-in-biological-drug-immune-responses/. Accessed December 3, 2020.
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