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Long-Term Outcome of Infliximab Optimization for Overcoming Immunogenicity in Patients with Inflammatory Bowel Disease

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Abstract

Background

Preliminary data suggest that treatment optimization can reverse immunogenicity and regain response in patients with IBD and secondary loss of response (SLR) to anti-TNF therapy due to antidrug antibodies. However, data regarding the long-term outcome of these patients are scarce.

Aims

We aimed to investigate drug retention in IBD patients of whom infliximab was optimized to overcome immunogenicity and variables associated with drug retention.

Methods

This was a retrospective, multicenter study of consecutive IBD patients with antibodies to infliximab (ATI), based on either proactive or reactive therapeutic drug monitoring, who underwent infliximab optimization (increasing dose, shortening interval, adding an immunomodulator, or combination) to overcome immunogenicity from September 2012 to July 2015; they were followed through December 2015. ATI were analyzed using the drug-tolerant Prometheus homogeneous mobility shift assay. Drug retention was defined as no need for drug discontinuation due to SLR or serious adverse event.

Results

Our cohort consisted of 22 patients (Crohn’s disease, n = 15). At the end of follow-up [median, (IQR): 17.3 (10.5–32.8) months] 77% (15/22) of patients were still on drug. Univariable Cox proportional hazards regression analysis identified first detectable ATI titer as the only variable associated with drug retention (HR: 0.89; 95% CI: 0.82–0.98, p = 0.016). Receiver-operating characteristic analysis identified an ATI titer < 8.8 U/mL associated with drug retention.

Conclusions

In real-life clinical practice, optimization of infliximab therapy can prevent drug discontinuation in approximately 3/4 of patients with ATI, especially in those with low titers. Large prospective studies are needed to confirm these data.

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Acknowledgments

K.P.: Ruth L. Kirschstein NRSA Institutional Research Training Grant (5T32DK007760-18).

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Author notes

  1. Mark T. Osterman and Adam S. Cheifetz have equally contributed to this work.

Authors and Affiliations

  1. Division of Gastroenterology, Center for Inflammatory Bowel Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA, 02215, USA

    Konstantinos Papamichael & Adam S. Cheifetz

  2. Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Ravy K. Vajravelu & Mark T. Osterman

Authors
  1. Konstantinos Papamichael
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  2. Ravy K. Vajravelu
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  3. Mark T. Osterman
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  4. Adam S. Cheifetz
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Contributions

KP contributed to study concept and design, data acquisition, analysis and interpretation, statistical analysis, and manuscript writing; RV involved in data acquisition and manuscript critical revision, and ASC and MTO contributed to study concept and design, data interpretation, and manuscript critical revision. All the authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Konstantinos Papamichael.

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Conflict of interest

A.S.C received consultancy fees from AbbVie, Janssen, Takeda, Ferring, Samsung, Miraca and Pfizer; M.T.O received consultancy fees from Janssen, AbbVie, UCB, Takeda, Pfizer, Merck, and Lycera and received research grant support from UCB; the remaining authors disclose no conflicts of interest.

Ethical standards

All procedures performed in the study were in accordance with the International Standard of Good Clinical Practice procedures and with the principles of the Declaration of Helsinki (1964) and relevant amendments. The protocol was approved by all institutional review boards and ethics committees at participating sites.

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Papamichael, K., Vajravelu, R.K., Osterman, M.T. et al. Long-Term Outcome of Infliximab Optimization for Overcoming Immunogenicity in Patients with Inflammatory Bowel Disease. Dig Dis Sci 63, 761–767 (2018). https://doi.org/10.1007/s10620-018-4917-7

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  • DOI: https://doi.org/10.1007/s10620-018-4917-7

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