Drug tolerant assays for anti-drug antibodies compared

Researchers of Sanquin developed new drug tolerant assays for anti-drug antibodies against biologicals. The ARIA, the Acid dissociation RadioImmunoAssay, was the most drug tolerant, even at higher drug concentrations.

Detection of anti-drug antibodies (ADA) is hampered by the presence of drug in regular tests. Researchers of Sanquin developed  three new drug-tolerant assays. They compared those to a previous one and to the ADA test that is standardly used in Sanquins Diagnostic department, the antigen binding test (ABT, a radioimmunoassay). All drug tolerant tests performed similarly. However, one of the newly developed test, the ARIA, outperformed the other drug tolerant tests at higher drug concentrations. 

“The ABT, currently used in our laboratory to measure ADAs, correlates nicely with the clinical response in patients” says Karien Bloem of Sanquin Biologcs. “However, drug tolerant assays could give insight into the early antibody formation and could identify  patients at risk for developing an excessive antibody response.  Next, to understand the immunological events that underlie immunogenicity, an unbiased test for antibody responses is crucial. For instance, we know that patients can develop tolerance upon continued treatment, so an initial antibody response may disappear in time. This may only come to light when using a drug-tolerant test”.

Antibodies in up to 66% of the adalimumab-treated patients

The researchers  measured anti-drug antibodies (ADA) to adalimumab in a cohort of adalimumab-treated rheumatoid arthritis patients using the various test formats. A surprisingly high percentage of the RA patients make antibodies to adalimumab, ranging from 51.1% to 66% in the drug tolerant tests, compared to 14.9% in the ABT. The ARIA (Acid dissociation RadioImmunoAssay) was slightly superior to the other formats. This test is a variation to the standard ABT, using an added acid dissociation step.

Consistent quantification

Bloem wants to stress that differences in reported incidence of antibody formation may be the result of differences in drug tolerance of the tests used. “For adalimumab this may vary from 1% to over 50 %. Drug tolerant assays could provide more consistent quantification of the amount of ADA formation in biological-treated patients”.

Journal of Immunological Methods, 2015 March