TDM. As is now widely appreciated, TLs of infliximab have been shown to correlate with clinical response, mucosal healing, and clinical remission. The TAXIT randomised, controlled study established that targeting infliximab TLs to 3-7 ug/mL, resulted in more efficient use of the drug (Xxxxx Xxxxxxxx et al., 2015a). An analysis of TL thresholds showed a progressive reduction in the proportion of patients not achieving remission at lower levels. The rates reduced from 25% at a level ≥1ug/mL, to 15% for those with a level ≥3ug/mL, 8% for levels ≥5 ug/mL, and 4% for levels ≥7 ug/mL. Notably, when these thresholds were analysed separately for CD and UC, the proportion of patients not in remission at each threshold was higher for UC than CD.
TDM. Data are emerging regarding the exposure-response relationship for vedolizumab, but the overall picture is still not entirely clear. Post-hoc analyses from all three GEMINI studies showed an exposure-response relationship for vedolizumab, for both UC, and CD. Quartile analyses of drug levels showed those in the highest quartiles had significantly higher rates of clinical response and remission during the induction and maintenance periods when compared to those in the lowest quartiles (Xxxxxx et al., 2013; Sandborn et al., 2013; Xxxxx et al., 2014). Studies have suggested that a week 6 TL is a potential predictor of the need for dose escalation (Xxxxxxx et al., 2017; Xxxxxx et al., 2018). In a study examining the relationship between TLs at week 2, 6 and 14 and rates of mucosal healing at week 52, only week 6 TLs correlated with rates of mucosal healing. Week 6 drug levels of 18 ug/mL and above correlated with higher rates of mucosal healing (Xxxxxx et al., 2018). Another study showed that week 6 levels <19 ug/mL were associated with the subsequent need for dose escalation (Xxxxxxx et al., 2017). These levels need further validation in larger studies and currently there is insufficient evidence to suggest a target therapeutic window for vedolizumab therapy. A recently presented abstract of a randomised trial (ENTERPRET) examined the benefit of vedolizumab dose escalation in patients with high drug clearance during induction in UC. Drug levels were measured at week 5 and patients who had levels of 30-50ug/mL were given twice the standard dose (300mg every 4 weeks, regimen A). Those who had levels of <30ug/mL were given four times the standard dose (600mg every 4 weeks, regimen B). The primary endpoint was endoscopic mucosal healing at week 30. There was no difference in the different treatment arms (18.9% of patients in the standard-dose arm vs 14.5% of patients in the combined dose-optimization arms (p=0.561). Rates of endoscopic mucosal healing at week 30 were also similar when standard dosing was compared with regimen A (p=0.612) and regimen B (p=0.666)(Xxxxx et al., 2022).
TDM. School shall maintain and implement the following Transportation Demand Management Plan ("TDM Plan"):
