Detection of adalimumab and antibodies to adalimumab using a homogeneous mobility shift assay.
OBJECTIVE
In 2013 a novel commercial test was launched (Anser1ADA 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.


CONCLUSIONS
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.
a University of Chicago Medicine , Chicago , IL , USA.
David T
DT
Rubin
b Clinical Development and Medical Affairs , Prometheus Laboratories Inc. , San Diego , CA , USA.
Snehal
S
Naik
b Clinical Development and Medical Affairs , Prometheus Laboratories Inc. , San Diego , CA , USA.
Venkateswarlu
V
Kondragunta
b Clinical Development and Medical Affairs , Prometheus Laboratories Inc. , San Diego , CA , USA.
Tharak
T
Rao
b Clinical Development and Medical Affairs , Prometheus Laboratories Inc. , San Diego , CA , USA.
Anjali
A
Jain
D000068879:Adalimumab / Q000097:blood / Q000276:immunology; D000328:Adult; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D016903:Drug Monitoring / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000276:immunology; D000069285:Infliximab / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric
D000906:Antibodies; D015415:Biomarkers; D000069285:Infliximab; D000068879:Adalimumab
Adalimumab; antibodies to adalimumab; antibodies to infliximab; homogeneous mobility shift assay; inflammatory markers; infliximab