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The AAPS Journal

, 20:35 | Cite as

Reporting, Visualization, and Modeling of Immunogenicity Data to Assess Its Impact on Pharmacokinetics, Efficacy, and Safety of Monoclonal Antibodies

  • Chaitali Passey
  • Satyendra Suryawanshi
  • Kinjal Sanghavi
  • Manish Gupta
Review Article

Abstract

The rapidly increasing number of therapeutic biologics in development has led to a growing recognition of the need for improvements in immunogenicity assessment. Published data are often inadequate to assess the impact of an antidrug antibody (ADA) on pharmacokinetics, safety, and efficacy, and enable a fully informed decision about patient management in the event of ADA development. The recent introduction of detailed regulatory guidance for industry should help address many past inadequacies in immunogenicity assessment. Nonetheless, careful analysis of gathered data and clear reporting of results are critical to a full understanding of the clinical relevance of ADAs, but have not been widely considered in published literature to date. Here, we review visualization and modeling of immunogenicity data. We present several relatively simple visualization techniques that can provide preliminary information about the kinetics and magnitude of ADA responses, and their impact on pharmacokinetics and clinical endpoints for a given therapeutic protein. We focus on individual sample- and patient-level data, which can be used to build a picture of any trends, thereby guiding analysis of the overall study population. We also discuss methods for modeling ADA data to investigate the impact of immunogenicity on pharmacokinetics, efficacy, and safety.

KEY WORDS

ADA antidrug antibodies immunogenicity neutralizing antibodies 

Notes

Acknowledgments

Professional medical writing and editorial assistance were provided by Stephan Lindsey, PhD, Melissa Kirk, PhD, and Cara Hunsberger at StemScientific, an Ashfield Company, funded by Bristol-Myers Squibb.

Research Support

This study was supported by Bristol-Myers Squibb.

Compliance with Ethical Standards

Conflict of Interest

C. Passey, S. Suryawanshi, K. Sanghavi, and M. Gupta are all employed by Bristol-Myers Squibb.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Chaitali Passey
    • 1
  • Satyendra Suryawanshi
    • 1
  • Kinjal Sanghavi
    • 1
  • Manish Gupta
    • 1
  1. 1.Clinical Pharmacology & PharmacometricsBristol-Myers SquibbPrincetonUSA

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