This blog post and tomorrow’s post highlights two articles on proactive therapeutic drug monitoring (pTDM) for inflammatory bowel disease. The first article (K Papmichael et al. Clin Gastroenterol Hepatol 2019; 17: 1655-68) summarizes a meeting of 13 international IBD specialists who reached consensus on 24 statements after a review of the literature.
- For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics.
- Reactive TDM was appropriate for all biologic agents both for primary non-response and secondary loss of response
Background/Rationale for pTDM:
- “Numerous studies have demonstrated a positive correlation between serum biologic drug.concentrations and favorable therapeutic outcomes”
- “Low or undetectable drug concentrations can lead to immunogenicity and treatment failures”
- “TDM…is an important tool for optimizing biologic therapy…Data suggest that pTDM, with drug titration to a target trough concentration, performed in patients with clinical response/remission can also improve the efficacy of anti-TNFs”
Table 4 Scenarios of Applying Therapeutic Drug Monitoring of Biological Therapy in Patients With Inflammatory Bowel Disease
- It is appropriate to order drug/antibody concentration testing in responders at the end of induction for all anti-TNFs.
- It is appropriate to order drug/antibody concentration testing at least once during maintenance for patients on all anti-TNFs.
- It is appropriate to order drug/antibody concentration testing of anti-TNFs at the end of induction in primary non-responders.
- It is appropriate to order drug/antibody concentration testing for all anti-TNFs in patients with confirmed secondary loss of response.
5-8: Vedolizumab -agreement only on ordering TDM in non-responders or those with loss of response
9-12: Ustekinumab -agreement only on ordering TDM in non-responders or those with loss of response
From Table 5: Biological Drug Concentrations and Anti-Drug Antibodies When Applying Therapeutic Drug Monitoring in Inflammatory Bowel Disease
- Infliximab: 15. In the presence of adequate trough drug concentrations, anti-drug antibodies are unlikely to be clinically relevant.
- Infliximab: 19. The minimal trough concentration for infliximab post-induction at week 14 should be greater than 3 μg/mL, and concentrations greater than 7 μg/mL are associated with an increased likelihood of mucosal healing.
- Adalimumab: 22. The minimum drug concentration at week 4 for adalimumab should at least be 5 μg/mL. Drug concentrations greater than 7 μg/ml are associated with an increased likelihood of mucosal healing.
- Certolizumab: 24 & 25: The minimum concentrations for certolizumab pegol at week 6 should be greater than 32 μg/mL and 15 μg/mL during maintenance.
- Golimumab 26 & 27: The minimum drug concentration at week 6 for golimumab should at least be 2.5 μg/mL and 1 μg/mL.during maintenance
My take: This article provides extensive literature to reinforce their recommendations. Most of the trough levels mentioned are minimum levels that need to be achieved.