PTH-091 Measurement of tnf-alpha drug levels and free versus total anti-drug antibodies using three commercially available assays
Bibliographic record
Abstract
Introduction Commercial assays are now available for therapeutic drug monitoring (TDM) of anti-TNF drugs and antibodies (ADAb). Utility of free versus total ADAb assays remains debatable, further complicated by lack of assay standardisation. Here we report analytical comparison of 3 commercially available assays for Infliximab (IFX) and Adalimumab (ADAL) drug levels (DL) and ADAb. Method Prospective evaluation of IFX and ADAL DL and ADAb was performed using our local LISA-TRACKER (LT) assay automated on e-Robot in IBD patients. Samples were also analysed by Immundiagnostik (IM, Germany) and Promonitor (PM, Spain) ELISA automated on Grifols Triturus. LT and PM utilises a specific bridging ELISA to quantitatively measure free-ADAb whereas IM utilises a dissociation step to enable detection of total-ADAb generating semi-quantitative results. IFX assays measure free drug but differ in microtitre plate coating and secondary detection reagents. Data was analysed using Passing Bablok and bias plots. LT and PM kits were provided at no cost. Results Summary of DL comparisons shown below: Samples analysed in different batches showed different kit biases against each other for IFX. Batch 1 showed that LT assay had 43.9% positive bias against ID kit whereas batch 2 demonstrated –26% negative bias. Both LT and ID kits used had different lot numbers. This change in bias was not observed in ADAL assays which showed consistent and systematic bias. PM kit showed concentration dependent bias changes within the same assay. 4 patients tested (n = 79) IFX ADAb positive with undectable DL with one exception where total/free ADAb was negative using ID and PM assays. A further 17 patients tested total ADAb positive using IM with detectable DL (0.5–9.2 ug/mL). 1 patient tested ADAL ADAb positive using LT, PM and ID assays however ID and PM assays produced positive resuts on a further 4 specimens, all with ADAL DL >5 ug/mL. Conclusion Although commercial assays are now available, our data highlights the need for assay standardisation. Free ADAb assays were in agreement however ADAb positivity was higher using ID assay. Significance of total ADAb positivity is unknown. Results for both IFX and ADAL confirm that DL are not transferable from one assay to another and as such, common therapeutic cut-offs will not be applicable. Further work is warranted to establish the cause of batch-to-batch variation observed. Disclosure of interest Z. Arkir: None Declared, N. Unsworth: None Declared, B. Warner: None Declared, G. Richards: None Declared, P. Irving Speaker Bureau of: MSD, Abbvie and Takeda.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".