Detection of adalimumab and antibodies to adalimumab using a homogeneous mobility shift assay

Abstract

Objective: In 2013 a novel commercial test was launched (Anser¹ ADA test) for the assay of serum adalimumab (ADL) and antibodies to adalimumab (ATA). This study aims to understand clinical practice patterns used with ADL in a real-world cross-sectional population.

Methods: Wilcoxon rank sum test, and linear and logistic regression methods were applied in the statistical analysis to test hypotheses. The study design was observational and uncontrolled.

Results: Of a total of 14,239 tests conducted, 5509 had information available that pertained to reasons for ordering, of which disease monitoring (46.9%) was the most common. Median serum ADL level with standard maintenance dosing (40 mg, biweekly) was 8.8 μg/mL (n = 2901). A five-fold decrease in median serum ADL levels occurred with very low ATA titers (1.7–3 U/mL, p < .0001). Serum ADL levels decreased further with ATA >7 U/mL (p < .0001). A total of 16.5% of patients were ATA positive, of whom 61.9% had low ATA (1.7–7 U/mL); 87.9% of ATA-positive patients had serum ADL levels ≤4.4 μg/mL. Expression of inflammatory markers significantly increased with high ATA (>7 U/mL). An inverse relationship between ADL and ATA was observed (R²: 0.49), and 4.1 μg/mL was identified as a cut-off that may segregate ATA-positive patients.

Conclusion: In this real-world cross-sectional population, serum ADL levels decreased with increasing ATA titers, with low ATA titers (≤7 U/mL) significantly reducing serum ADL compared to ATA-negative samples. Expression of inflammatory markers significantly increased at higher ATA titers (>7 U/mL). These findings highlight the clinical importance of monitoring patients for drug levels and anti-drug antibody titers.

Keywords:

• Adalimumab
• antibodies to adalimumab
• antibodies to infliximab
• homogeneous mobility shift assay
• inflammatory markers
• infliximab

Note

Transparency

Declaration of funding

This study was funded by Prometheus Laboratories Inc. The preparation of this paper was funded by Prometheus Laboratories Inc.

Author contributions: D.T.R., T.R., V.K., A.J. and S.N. were involved in the conception and design of the study. All authors were involved in analysis and interpretation of the data and the critical revision of the paper. All authors have approved the final version of this paper for publication and agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

D.T.R. has disclosed that, in the past 12 months, he has received grant support from AbbVie, Genentech, Janssen Pharmaceuticals Inc., Prometheus Laboratories Inc., Shire, Takeda Pharmaceutical Co. Ltd., and UCB Pharma; he has served as a consultant for AbbVie, Amgen Inc., Emmi Solutions, Genentech, Janssen Pharmaceuticals Inc., Pfizer Inc., Prometheus Laboratories Inc., Shire, Takeda Pharmaceutical Co. Ltd., and UCB Pharma; he is co-founder of the nonprofit medical education entity Cornerstones Health Inc., and is co-founder of GoDuRn LLC; he is a member of the Board of Trustees of the American College of Gastroenterology. S.N., V.K., T.R., and A.J. have disclosed that they are employees of Prometheus Laboratories Inc.

Acknowledgments

Writing support was provided by Dr. Anthony Stonehouse of Watson & Stonehouse Enterprises LLC and was funded by Prometheus Laboratories Inc.

Notes

1 Anser is a registered trade name of Prometheus Laboratories Inc., San Diego, CA, USA