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Therapeutic Drug Monitoring in Inflammatory Bowel Disease: Optimising Therapeutic Effectiveness of Biologics

  • Ashish Srinivasan
  • Nik Sheng Ding
  • Daniel van Langenberg
  • Peter De Cruz
Chapter

Abstract

Biologic therapies have proven effective in inducing and maintaining remission across both Crohn’s disease (CD) and ulcerative colitis (UC). Treatment algorithms incorporating therapeutic drug monitoring (TDM), including assessment of drug levels and antidrug antibodies (ADA), have been advocated to improve outcomes.

The utility of TDM is increasingly recognised; however, there has been much debate regarding the benefits of a reactive versus proactive approach to measuring drug levels to guide intervention. Several studies have documented favourable clinical, biochemical and endoscopic outcomes with higher drug levels. Although TDM targets to achieve clinical remission during maintenance anti-tumour necrosis factor-α (anti-TNF) therapy are well developed, an evidence-based approach to utilise TDM to assess and intervene following anti-TNF induction is lacking. Furthermore, studies have documented that higher drug levels should be targeted to achieve more stringent endpoints such as mucosal healing, with higher and/or accelerated biologic dosing strategies demonstrating improved outcomes across clinically aggressive inflammatory bowel disease (IBD) subtypes such as perianal fistulising CD and acute severe UC.

Despite their efficacy, a proportion of patients will demonstrate primary non-response (PNR) and secondary loss of response (SLOR) to biologic therapy, with immunogenicity emerging as an important cause. Understanding the mechanism through which biologic loss of response occurs remains important in directing subsequent therapeutic decisions such as dose escalation, switching biologic agents or classes and considering the addition of immunomodulator co-therapy. Preliminary data also reassuringly suggests that the principles of anti-TNF TDM are broadly applicable across newer agents such as vedolizumab and ustekinumab. As treat-to-target algorithms continue to evolve, they should strive to integrate induction and maintenance TDM targets specific to both the disease phenotype and target endpoints.

This chapter will concentrate on aspects of TDM in biologics within IBD, with a particular focus on infliximab and adalimumab given the vast majority of currently published data exists for these agents.

Keywords

Therapeutic drug monitoring Anti-TNF Infliximab Adalimumab Inflammatory bowel disease Ulcerative colitis Crohn’s disease 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ashish Srinivasan
    • 1
    • 2
    • 3
  • Nik Sheng Ding
    • 4
    • 5
    • 6
  • Daniel van Langenberg
    • 7
    • 8
  • Peter De Cruz
    • 9
    • 10
  1. 1.Department of GastroenterologyAustin HealthMelbourneAustralia
  2. 2.Department of GastroenterologyEastern HealthMelbourneAustralia
  3. 3.Monash University, Department of MedicineMelbourneAustralia
  4. 4.St Vincent’s HospitalMelbourneAustralia
  5. 5.The University of MelbourneMelbourneAustralia
  6. 6.Imperial CollegeLondonUK
  7. 7.Department of GastroenterologyEastern HealthMelbourneAustralia
  8. 8.Monash University, Department of MedicineMelbourneAustralia
  9. 9.Department of GastroenterologyAustin HealthMelbourneAustralia
  10. 10.Department of MedicineThe University of MelbourneMelbourneAustralia

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