A recent retrospective study (S Lega et al. Inflamm Bowel Dis 2019; 25: 134-41) suggests that proactive therapeutic drug monitoring (pTDM) with infliximab (IFX) helps achieve similar outcomes as combination therapy (with immunomodulator) in patients with inflammatory bowel disease.
Before reviewing the key findings, it is important to emphasize a few crucial limitations/methods:
- The study enrolled 83 patients; only 16 received were in the monotherapy pTDM group.
- This was a retrospective study
- The authors utilized TDM at week 10. If the IFX level was <20 mcg/mL, the dose and frequency of infliximab were both adjusted. If the level was between 20 & 25, either the frequency was adjusted or no adjustment, and if the level was >25, then no adjustment in dosing was performed.
- The frequency of infliximab discontinuation with mono therapy in those with pTDM was lower than in those with ‘standard of care’ TDM (P=0.04) but did not differ from patients receiving combination therapy
- Overall 9 of the 83 patients (11%) discontinued IFX during the 1-year study
In the discussion, the authors suggest that week 14 TDM may be suboptimal as this is the first time patients have an 8-week interval.
My take: The jury is out with regard to whether pTDM can negate the need for combination therapy –a prospective trial is needed; however, the idea of getting TDM a bit earlier is intriguing, particularly as it has been shown that a high percentage of pediatric patients are receiving an insufficient dose of infliximab (Is Standard Infliximab Dose Tool Low in Pediatrics?)
Key words: 10 weeks, therapeutic drug monitoring, infliximab, trough
Related blog posts:
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
View from Artist’s Drive, Death Valley
A recent clinical review (X Roblin et al. Inflamm Bowel Dis 2018; 24: 1904-9) examines the utility of proactive drug monitoring of anti-TNF therapy in inflammatory bowel disease.
The authors note that several observational trials suggested that proactive drug monitoring would help optimize the effect of anti-TNF therapy, especially infliximab. However, two randomized controlled clinical trials, TAXIT (n=273) and TAILORIX (n=122), were not able to show long-term benefit from proactive therapeutic monitoring.
At the same time, the authors note that a recent trial (Ungar B et al. Clin Gastroenterol Hepatol 2016; 14: 550-7, e2) has shown that infliximab trough levels >5 mcg/mL and adalimumab levels >7.2 mcg/mL identified mucosal healing with 85% specificity. Higher cutoffs showed only minimal further increase in mucosal healing rates.
My take: To this point, controlled trials have not shown that proactive drug monitoring of anti-TNF therapy is beneficial; this review explains the design and limitations of these studies. My personal view is that more studies are needed to know if proactive drug monitoring is worthwhile. Proactive drug monitoring may be more useful in children/adolescents than adults due to much greater variation in size and dosing.
A recent commentary on therapeutic drug monitoring (from KT Park Twitter Feed): Therapeutic Targets in IBD
Related blog posts:
Moraine Lake, Banff
This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.
Here is a link to postgraduate course syllabus: NASPGHAN PG Syllabus – 2017
Therapeutic Drug Monitoring
Andrew Grossman Children’s Hospital of Philadelphia
The topic of therapeutic drug monitoring, both reactive and proactive, has been discussed numerous times on this blog. This talk provided a good review of this topic.
- Greatest predictor of infliximab treatment failure was a low infliximab (<0.9 mcg/mL at anytime or <2.2 mcg/mL at 14 weeks) (Castelle et al Am J Gastro 2013; 108: 962-71)
- Low level antibodies to infliximab may be transient in ~28% and may be overcome with escalation of therapy
- Tissue levels of infliximab (and other agents) may be inadequate despite good serum levels
What if anti-TNF fails
Maria Oliva-Hemker Johns Hopkins University School of Medicine
- Discussed prevalence of problem with anti-TNF failures and main options: vedolizumab, ustekinumab, and surgery
- Vedolizumab can take a while to work, particularly for Crohn’s disease
- Limited data in pediatrics for these newer agents
- Ustekinumab has some preliminary data indicating benefit with anti-TNF induced psoriaform rashes
- Newer agents also likely to need therapeutic drug monitoring
- Overall, ustekinumab and vedolizumab have good safety profiles at this point
Prevention of postoperative Crohn’s disease
Miguel Regueiro University of Pittsburgh
- Rationale for postoperative preventative treatment: high rate of recurrent disease which can be silent for several years despite progressive damage to GI tract
- Large study (PREVENT) to compare infliximab and placebo after surgery. Primary endpoint was clinical recurrence (was endpoint demanded by FDA) even though clinical recurrence can be a late finding. Endoscopic recurrence rate was a secondary endpoint.
Dr. Regueiro’s approach
- Low risk patient –repeat scope at 6 months post-op, then every 1-3 yrs if no disease and Rx with anti-TNF or immunomodulator in those with endoscopic recurrence
- Moderate risk patient -possible use of thiopurine or use the ‘low risk’ approach
- High risk patient-combination therapy and if doing well for several years, consider monotherapy
- In pediatrics, the postoperative management is unclear due to difficulty with risk stratification. If postoperative treatment is not given, consider colonoscopy 3-4 months afterwards and treat if recurrence. Then could use calprotectin every 3 months to monitor and when >50, likely will need to be treated
PREVENT Trial Data: