Comparisons of Serum Infliximab and Antibodies-to-Infliximab Tests Used in Inflammatory Bowel Disease Clinical Trials of Remicade®.
Monitoring infliximab (IFX) concentrations and antibodies-to-IFX (ATI) titers during inflammatory bowel disease treatment may allow more informed decisions in assessing exposure/response and determining appropriate dosing. To aid in interpreting results from different commercial tests in the context of Janssen's published Remicade® results, the reliability of Janssen's IFX and ATI assays was compared with commercial assays from KU Leuven, Sanquin, Dynacare, and LabCorp. Test results were independently reported to Janssen. All assays were tested for specificity, selectivity, and precision. ATI assays were evaluated for sensitivity, drug interference, and potential interference of tumor necrosis factor-alpha (TNF-α). IFX assays were specific, accurate, and reproducible. Intra-class correlation of Janssen IFX assay results with those from KU Leuven, Sanquin, Dynacare, and LabCorp were 0.960, 0.895, 0.931, and 0.971, respectively. ATI titers >10 interfered with IFX assessment in all IFX assays, whereas TNF-α (≤50 ng/mL) did not interfere with IFX detection in any assay. ATI assays specifically and reproducibly detected ATI. Janssen, Sanquin, and LabCorp ATI methods were more resistant to IFX interference than Dynacare and KU Leuven, which were affected by IFX concentrations at ≥2 μg/mL. TNF-α (<5 ng/mL) did not interfere with ATI detection. Strong agreement was observed between Janssen's IFX and ATI assays and the diagnostic service provider assays. Our study results indicate that all four commercially available assays are suitable for therapeutic drug monitoring of IFX. The substantial agreement reported here between the comparator assays and the Janssen drug-tolerant assay provides support to clinicians in their use of these commercial assays, and for understanding their patients' IFX and ATI results relative to published data from clinical studies of Remicade.
Biologics Development Sciences, Janssen Research & Development, LLC, Spring House, PA, USA.
Joseph C
JC
Marini
Nonclinical Statistics, Janssen Research & Development, LLC, Spring House, PA, USA.
Jocelyn
J
Sendecki
Janssen Biologics BV, Leiden, The Netherlands.|Medical Affairs, Immunology, MSD International, Kriens, Switzerland.
Freddy
F
Cornillie
Medical Affairs, Janssen Scientific Affairs, LLC, Horsham, PA, USA.
John W
JW
Popp
Medical Affairs, Janssen Scientific Affairs, LLC, Horsham, PA, USA.
Shawn
S
Black
Medical Affairs, Janssen Scientific Affairs, LLC, Horsham, PA, USA.
Marion
M
Blank
Department of Pharmaceutical Sciences, KU Leuven, Leuven, Belgium.
Ann
A
Gils
Department of Pharmaceutical Sciences, KU Leuven, Leuven, Belgium.
Thomas
T
Van Stappen
Sanquin Diagnostic Services, Amsterdam, The Netherlands.
Dörte
D
Hamann
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
Theo
T
Rispens
Dynacare, Laval, Quebec, Canada.
Lina
L
Thérien
LabCorp, Calabasas Hills, CA, USA.
Kelly
K
Chun
Biologics Development Sciences, Janssen Research & Development, LLC, Spring House, PA, USA. GShanka3@its.jnj.com.
Gopi
G
Shankar
D000906:Antibodies / Q000097:blood* / Q000276:immunology; D002986:Clinical Trials as Topic; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D000069285:Infliximab / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
antibodies-to-infliximab; electrochemiluminescence immunoassay (ECLIA); enzyme-linked immunosorbent assay (ELISA); inflammatory bowel disease; infliximab