Background/Purpose:

A reduced clinical response in patients taking TNF-alpha inhibitors is influenced by their immunogenicity and therefore the importance of therapeutic drug monitoring has been increasingly recognized in the recent years. Many different methods used in routine analysis of anti-drug antibodies (ADA) differ in their reported levels and types of the detected antibodies. Bridging ELISA (bELISA), mostly used in routine analysis, cannot differentiate between neutralizing and non-neutralizing ADA and cannot detect IgG4, which is possible with competitive ELISA (cELISA) and Reporter Gene Assay. The latter is costly and labour-intensive, while cELISA is only emerging. It has been clinically observed that many patients with negative bELISA lose response over time despite dose optimisation.

We aimed to test whether cELISA detects anti-adalimumab (anti-ADL) antibodies in patients negative in bELISA and if anti-ADL antibodies, as detected by cELISA, can better predict a subsequent loss of response compared to bELISA.

Methods:

Sera of patients with inflammatory bowel or chronic rheumatic diseases treated with ADL, having undetectable ADL levels and negative anti-ADL levels in bELISA, were collected and tested with in-house cELISA (sampling time). Only samples from patients who continued with the therapy were included, meaning they had received at least one more application of the drug after sampling time (n=16).

In cELISA, samples were incubated with a fixed amount of added drug and the neutralizing capacity of the samples was determined using a plate with pre-coated TNF-alpha. Kaplan-Meier analysis and Log Rank test were performed in order to make a comparison between the group of samples negative in both assays and the group of samples negative in bELISA, but positive in cELISA, according to clinical status on follow-up (observation time).

Results:

The samples negative in bELISA were all subsequently tested by cELISA whereby 5/16 were detected as positive and 11/16 as negative samples. Follow-up of patients revealed an 80% loss of response in patients with negative bELISA and positive cELISA, and a 45% loss of response in patients negative for both ELISAs. The Kaplan-Meier analysis and Log Rank test both showed statistically significant differences between the group of samples negative in both assays and the group of samples negative in bELISA, but positive in cELISA (p=0.024). Patients with positive cELISA experienced a shorter time period before treatment failure compared to patients negative in both assays.

Conclusion:

Positive anti-ADL antibodies in cELISA can predict treatment failure in patients taking ADL, who had undetectable levels of ADL and negative anti-ADL antibodies, as detected by bELISA. Thus, cELISA shows clear benefit for clinical utility over bELISA alone.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-drug-antibodies-detected-by-competitive-elisa-can-predict-treatment-failure-in-patients-taking-adalimumab/