Issue 04

Clinical Question

Are low vedolizumab (VDZ) trough levels during induction predictive of the need for dose optimization?

Editor’s Bottom Line

Low VDZ serum trough levels (<19 μg/mL) at week 6 of induction predict loss of response. Dose optimization at that point can turn a non-responder into a responder.

Editorial Note

Similar findings have been reported for anti-TNF agents. Measurement of biologic levels during induction as a predictor of response is not yet standard of care and should be reserved for clinical research studies. However, it does give us insight into how levels during induction could be used as a precision health tool to individually optimize therapy. Hopefully, we will have definitive answers during 2017 to move this practice into standard of care.

Reference

Williet N, Boschetti G, Fovet M, et al. Association between low trough levels of vedolizumab during induction therapy for inflammatory bowel diseases with need for additional doses within 6 months. Clin Gastroenterol Hepatol. 2016 Nov 24. [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pubmed/27890854

Synopsis

Enrolled patients had previously failed two anti-TNFs and were now on tapering steroid therapy. VDZ was given as 300 mg IV at weeks 0, 2, 6, and then every 8 weeks. VDZ trough level was measured at week 6.

• If no clinical response at week 6, treatment was optimized with another infusion at week 10 and then every 4 weeks
• In case of loss of response, a similar optimization regimen was used.

Study end point was an association between serum trough levels of VDZ during induction at week 6 with need for subsequent dosing increase within 6 months.

Of 47 patients who started on VDZ, by week 6 there were 30 patients (CD=23; UC=7) who had significantly lower than expected trough serum levels (23.0 μg/mL [14.0-37.0] vs. 42.5 μg/mL [33.5-50.7]). These 30 patients needed the optimized dosing regimen to regain response within 6 months. Patients who had optimized dosing at week 10, achieved clinical remission 4 weeks later. Based upon receiver operating characteristics, if serum trough levels during the 6 weeks of induction were below 19 μg/mL, there was a 100% positive predictive value that optimized dosing was required within the first 6 months to regain response.

Details

Study Design: Observational study
Funding: None
Allocation: n/a
Setting: France
Level of Evidence: 2b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.