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Antidrug antibody detection for adalimumab depends on the type of assay used: an experimental approach to help clinicians interpret diagnostic data
J. Ruwaard1, A.F. Marsman2, M.T. Nurmohamed3, I.E. Van der horst-Bruinsma4, H. Te Velthuis5, K. Bloem6, A. De Vries7, T. Rispens8, G. Wolbink9
- Amsterdam Rheumatology and Immunology Center, location Reade, Amsterdam, the Netherlands. j.ruwaard@reade.nl
- Amsterdam Rheumatology and Immunology Center, location Reade, Amsterdam, the Netherlands.
- Amsterdam Rheumatology and Immunology Center, location Reade and location VU Medical Center, Amsterdam, the Netherlands.
- Amsterdam Rheumatology and Immunology Center, location VU Medical Center, Amsterdam, the Netherlands.
- Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, Amsterdam, the Netherlands.
- Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, and Biologics Laboratory, Diagnostic Services Sanquin, Amsterdam, the Netherlands.
- Biologics Laboratory, Diagnostic Services Sanquin, Amsterdam, the Netherlands.
- Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, Amsterdam, the Netherlands.
- Amsterdam Rheumatology and immunology Center, location Reade, and Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, Amsterdam, the Netherlands.
CER11573
2019 Vol.37, N°5
PI 0756, PF 0761
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PMID: 30943139 [PubMed]
Received: 01/08/2018
Accepted : 19/11/2018
In Press: 18/03/2019
Published: 29/08/2019
Abstract
OBJECTIVES:
To compare different methods of antidrug antibody (ADA) against adalimumab detection in ankylosing spondylitis (AS) patients and the impact of ADA on adalimumab drug levels and mean ASDAS-CRP.
METHODS:
We used the acid-dissociation-radioimmunoassay (ARIA), antidrug-binding-test (ABT) and a bridging Enzyme-linked Immunosorbent Assay (ELISA) to detect ADA at 4, 12 and 24 weeks of treatment. Patients were divided into groups; all assays negative (All-neg), only ARIA positive (ARIA-only-pos), ARIA and ABT positive, bridging ELISA negative (ARIA/ABT-double-pos) and all assays positive (All-pos).
RESULTS:
Eighty-three consecutive AS patient were included. At week 4, 18% compared to 11% and 0% of the patients tested positive for ADA in the ARIA, ABT and bridging ELISA, respectively. At week 12 and 24, cumulative 52% and 69% patients tested positive in the ARIA, compared to 27% and 30% patients in the ABT and 2% patients in the bridging ELISA. Adalimumab levels between All-neg and ARIA-only-pos were 9.1 (5.5-12.5) and 8.5 (5.7-12.3). Drug levels differed between ARIA/ABT-double-pos (2.7 (1.3-4.4)) and All-neg (9.1 (5.5-12.5)). All-pos patients had undetectable drug levels. Mean ASDAS-CRP at week 24 differs between All-neg (1.9 (±1.2)), and All-pos (3.8 (±1.9)) and ARIA/ABT-double-pos (2.0 (±1.1)) and All-pos.
CONCLUSIONS:
The majority of AS patients had detectable ADA against adalimumab in the ARIA. The ARIA detects more ADA compared to the less drug tolerant ABT and bridging ELISA. The clinical relevance depends on the impact on the bio-availability of the drug. A drug level measurement therefore helps to interpret ADA data regardless of type of assay used.
