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  • Review Article
  • Published:

Tailoring anti-TNF therapy in IBD: drug levels and disease activity

Key Points

  • Immunogenicity is an important, but not the sole, factor affecting anti-TNF drug clearance and efficacy

  • Correct interpretation of drug and anti-drug antibodies results requires consideration of the clinical context, the assay used and the various mechanisms that affect drug pharmacokinetics and pharmacodynamics as well the disease activity

  • Assessment of disease activity along with measurements of anti-TNF drug levels facilitates rational decisions on management of loss of response, optimization of disease control during maintenance therapy and possible cessation of treatment

  • Anti-drug antibody measurements might aid in these clinical situations, but are mostly useful in patients with loss of response for choosing the next-step intervention

Abstract

The treatment of IBD with anti-TNF agents has substantially evolved since their first introduction more than a decade ago. The robust efficacy witnessed in many patients has raised new questions pertaining to the observation of subgroups of patients who fail to respond or who lose response to these otherwise very effective drugs. Conversely, the exorbitant cost of biologic agents coupled with their efficacy in inducing lasting remission has introduced new concepts addressing the possibility of therapy cessation in some patients after deep remission has been achieved. Measuring drug and anti-drug antibody (ADA) levels which develop in some patients has emerged as a valuable tool in understanding the mechanisms responsible for some of these clinical scenarios. However, knowledge on how to use these measurements to guide clinical decisions in daily practice is still in its nascency and awaits prospective validation trials. Furthermore, as described in this Review, knowledgeable interpretation of drug and ADA test results mandates understanding the interplay between the technical profile of the assay used, the timing of the measurement in the drug cycle, assessment of disease activity, and the profoundly different pharmaco-clinical scenarios that can culminate in a similar test result.

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Figure 1: A proposed algorithm for managing loss of response.

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Acknowledgements

The work of the authors is supported in part by the 'Talpiot' medical leadership grant from the Sheba Medical Center (to S. Ben-Horin), the Legacy heritage foundation from the Rambam Health Care Campus (to Y. Chowers), and the Helmsley charitable fund (to S. Ben-Horin & Y. Chowers).

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S. Ben-Horin researched data, discussed content, wrote and reviewed/edited the manuscript before submission. Y. Chowers discussed content, wrote and reviewed/edited the manuscript before submission.

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Correspondence to Shomron Ben-Horin.

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S. Ben-Horin and Y. Chowers have received consultancy fees from Abbot, Schering-Plough and Janssen.

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Ben-Horin, S., Chowers, Y. Tailoring anti-TNF therapy in IBD: drug levels and disease activity. Nat Rev Gastroenterol Hepatol 11, 243–255 (2014). https://doi.org/10.1038/nrgastro.2013.253

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