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The Natural History of Infliximab Immunogenicity and the Effect on Pharmacokinetics and Clinical Outcomes: A Prospective Pediatric Crohn Disease Cohort Study

Colman, Ruben J, M.D.
http://orcid.org/0000-0001-9891-8570
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1623239846522151

Abstract Details

2021, MS, University of Cincinnati, Medicine: Clinical and Translational Research.
Background: Antibodies to infliximab (ATIs) are associated with secondary loss of response (LOR) and can constitute a risk for drug reactions. Limited studies have associated ATIs with increased infliximab clearance. We aimed to assess the impact of ATIs on infliximab clearance and LoR during the first year of therapy in a real-world Crohn disease (CD) cohort. Methods: This multicenter prospective cohort collected peak and trough serum infliximab/ATI concentrations during the first year of infliximab therapy. Clinical remission (CR) was defined as a weighted Pediatric CD Activity Index (wPCDAI) <12.5 without corticosteroids. LoR was defined as wPCDAI =12.5 for =2 infusions when previously in CR. Infliximab clearance was estimated using data from 660 infusions and compared between pre-ATI, during ATI, and following ATI resolution by MANOVA. Optimal cut off for ATI resolution was determined by receiver operating characteristic curves. Results: ATIs were detected in 68% (53/78) patients (range of 23-1828 ng/mL), with 26% (14/53) ATI >200 ng/mL. Median clearance in ATI+ was 0.0111 L/h compared to 0.0094 L/h with absent ATI (p<0.001). Among ATI+ patients, those with LoR had accelerated CL compared to patients without LoR (0.0145L/h vs. 0.0100L/h; p<0.001). A maximum ATI level of =99 ng/mL predicted ATI resolution (AUROC 0.80 [95% CI 0.64-0.96]; sensitivity 75%; specificity 70%). Conclusions: In this real-world cohort, ATIs as low as 23 ng/mL were shown to impact drug clearance. These data support active management for even low-level ATI to improve infliximab clearance and prevent LOR.
Scott Langevin, Ph.D. (Committee Chair)
Phillip Minar (Committee Member)
Nicholas Ollberding (Committee Member)
29 p.
Surgery
Immunogenicity; anti-TNF therapy; anti-drug antibodies; pharmacokinetics; inflammatory bowel diseases; model-informed precision dosing

Recommended Citations

Citations

  • Colman, M.D., R. J. (2021). The Natural History of Infliximab Immunogenicity and the Effect on Pharmacokinetics and Clinical Outcomes: A Prospective Pediatric Crohn Disease Cohort Study [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1623239846522151

    APA Style (7th edition)

  • Colman, M.D., Ruben. The Natural History of Infliximab Immunogenicity and the Effect on Pharmacokinetics and Clinical Outcomes: A Prospective Pediatric Crohn Disease Cohort Study. 2021. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1623239846522151.

    MLA Style (8th edition)

  • Colman, M.D., Ruben. "The Natural History of Infliximab Immunogenicity and the Effect on Pharmacokinetics and Clinical Outcomes: A Prospective Pediatric Crohn Disease Cohort Study." Master's thesis, University of Cincinnati, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1623239846522151

    Chicago Manual of Style (17th edition)

ucin1623239846522151
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This open access ETD is published by University of Cincinnati and OhioLINK.