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Comparisons of Serum Infliximab and Antibodies-to-Infliximab Tests Used in Inflammatory Bowel Disease Clinical Trials of Remicade®

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ABSTRACT

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.

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ACKNOWLEDGMENTS

The authors would like to acknowledge Shannon Rebarchak, Shannon Dogmanits, Kathryn Durham (Janssen Research & Development, LLC), and Stacey Buist (formerly of Janssen Scientific Affairs, LLC) for their contributions to the study and the analyses. Writing and editorial support was provided by Kirsten Schuck Gross, BS and James P. Barrett, BS, of Janssen Scientific Affairs, LLC.

Author information

Author notes

  1. Freddy Cornillie

    Present address: Medical Affairs, Immunology, MSD International, Kriens, Switzerland

Authors and Affiliations

  1. Biologics Development Sciences, Janssen Research & Development, LLC, Spring House, PA, USA

    Joseph C. Marini & Gopi Shankar

  2. Nonclinical Statistics, Janssen Research & Development, LLC, Spring House, PA, USA

    Jocelyn Sendecki

  3. Janssen Biologics BV, Leiden, The Netherlands

    Freddy Cornillie

  4. Medical Affairs, Janssen Scientific Affairs, LLC, Horsham, PA, USA

    John W. Popp Jr., Shawn Black & Marion Blank

  5. Department of Pharmaceutical Sciences, KU Leuven, Leuven, Belgium

    Ann Gils & Thomas Van Stappen

  6. Sanquin Diagnostic Services, Amsterdam, The Netherlands

    Dörte Hamann

  7. Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands

    Theo Rispens

  8. Dynacare, Laval, Quebec, Canada

    Lina Thérien

  9. LabCorp, Calabasas Hills, CA, USA

    Kelly Chun

Authors
  1. Joseph C. Marini
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Corresponding author

Correspondence to Gopi Shankar.

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Conflicts of Interest

Authors’ declaration of personal interests: T. Van Stappen is a PhD fellow of the Agency for the Promotion and Innovation by Science and Technology in Flanders (IWT, Flanders). A. Gils received lecture fee(s) from MSD, Pfizer, AbbVie, and Janssen Biologicals; consultant fees from UCB and institution licensed the infliximab ELISA to apDia. F. Cornillie is a former employee of Janssen Biologics, BV and is a current employee of MSD International. K. Chun is an employee of LabCorp. L. Thérien was an employee of Dynacare at the time the study was conducted. D. Hamann is an employee of Sanquin. T. Rispens is an employee of Sanquin and has received lecture fees from Pfizer and AbbVie. J. Marini, J. Sendecki, and G. Shankar are employees of Janssen Research & Development, LLC. S. Black and M. Blank are employees of Janssen Scientific Affairs, LLC.

This study was funded by Janssen Scientific Affairs, LLC (Horsham, PA). This study was designed and conducted by KU Leuven, LabCorp, Dynacare, Sanquin, Janssen Scientific Affairs, LLC, and Janssen Research & Development, LLC who jointly analyzed and interpreted the data, and contributed to the manuscript.

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Marini, J.C., Sendecki, J., Cornillie, F. et al. Comparisons of Serum Infliximab and Antibodies-to-Infliximab Tests Used in Inflammatory Bowel Disease Clinical Trials of Remicade®. AAPS J 19, 161–171 (2017). https://doi.org/10.1208/s12248-016-9981-3

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  • DOI: https://doi.org/10.1208/s12248-016-9981-3

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