The optimal management of anti-drug antibodies to infliximab and identification of anti-drug antibody values for clinical outcomes in patients with inflammatory bowel disease

Abstract

Purpose

Secondary loss of response (LOR) to infliximab (IFX) commonly occurs. One cause is the development of anti-drug antibodies (ADAs). Evidence regarding the optimal management of ADAs is lacking. We aim to identify the best practice of management of ADAs to IFX to avoid discontinuation of therapy and to determine specific ADA cut-off values to determine pre-specified clinical outcomes.

Methods

This is a 3-year study of patients receiving IFX who developed ADAs > 8μg/ml. We reviewed the management strategies and subsequent outcomes in patients who developed ADAs.

Results

A total of 132 patients are included. Baseline characteristics include 54% male patients and mean age of 39.4 years. Fifty-two percent (n = 69) of patients discontinued IFX following the development of ADAs, 33.3% (n = 44) sited as secondary to LOR. Both an increase in IFX and adjustments to combination therapy were associated with lower rates of discontinuation of IFX vs no intervention (p value < 0.001, p value < 0.001). An increase in IFX resulted in a significant difference in ADAs/IFX trough levels pre- and post-intervention (p value < 0.001, p value = 0.032). ROC curve analysis yielded significant cut-off values for ADAs and treatment failure (ADA >16μg/ml, AUC 0.642, p value 0.003), steroid use (ADA >19 μg/ml, AUC 0.61, p value 0.048) development of infusion reactions (ADA> 37 μg/ml, AUC 0.68, p value 0.045) and switch to another biologic (ADA >45 μg/ml, AUC 0.739, p value <0.001).

Conclusion

Both escalation of IFX and combination therapy resulted in lower rates of LOR. ROC curve analysis identified significant cut-off values for ADA trough levels and important clinical outcomes.

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Acknowledgements

The authors would like to thank the Inflammatory Bowel Disease Unit in Beaumont Hospital for supporting the undertaking of this study.

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Authors

Contributions

Neasa Mc Gettigan—data collection, analysis, report, and submission of the study, and responsible for overall content

Aman Shah Afridi—data collection

Grace Harkin—data collection

Caroline Lardner—data collection

Stephen Patchett—data collection and planning

Danny Cheriyan—data collection and planning

Gavin Harewood—data collection and planning

Karen Boland—data collection and planning

Aoibhlinn O’Toole—planning, article revision, and responsible for overall content

Corresponding author

Correspondence to Neasa Mc Gettigan.

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Approval was obtained from the Beaumont Hospital Quality improvement committee to perform the study. Consent was not required as part of the study given the retrospective nature and complete anonymity of the date recorded.

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Mc Gettigan, N., Afridi, A.S., Harkin, G. et al. The optimal management of anti-drug antibodies to infliximab and identification of anti-drug antibody values for clinical outcomes in patients with inflammatory bowel disease. Int J Colorectal Dis (2021). https://doi.org/10.1007/s00384-021-03855-4

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Keywords

  • Biologics
  • Ulcerative colitis
  • Crohn’s disease
  • Immunogenicity