Proactive therapeutic drug monitoring improves clinical outcomes in patients with inadequate post-induction infliximab trough levels

Abstract Background A large body of evidence demonstrates a significant correlation between week 14 infliximab trough levels (IFXTL) and several clinical outcomes. In patients with low IFXTL at week 14, proactive therapeutic drug monitoring (TDM) may potentially improve clinical results. Methods Retrospective study including 181 patients (63.5% with Crohn’s disease) under proactive TDM. IFXTL were measured at week 14 and every 2 infusions using a drug sensitive assay (Theradiag®, Lisa Tracker) with treatment proactively escalated to an IFXTL 5–10 ug/ml. We compared the clinical outcomes between patients with low (<5 ug/ml) and adequate IFXTL at week 14, in respect to clinical remission, fecal calprotectin (Fc) remission, C-reactive protein (CRP) remission, hospitalization, treatment discontinuation, and surgery up to 1 year of follow-up. Results Ninety-one patients (50.3%) had low IFXTL at week 14. These patients presented lower rates of clinical remission (69.2% vs 82.2%, P=0.031), Fc remission (41.9% vs 73.4%, P<0.001), and CRP remission (60.7% vs 72.7%, P= 0.061) at week 14 of treatment. Likewise, worse outcomes were also shown by the end of the study, with lower rates of clinical remission (64.8% vs 87.8%, P<0.001), and Fc remission (58.9% vs 77.9%, P=0.005), and higher rates of hospitalization (17.6% vs 6.7%, P=0.021), surgery (5.5% vs 0%, P=0.030), treatment discontinuation (36.3% vs 17.8%, P=0.004), and any unfavorable outcome (42.9% vs 21.1%, P=0.001). Following proactive treatment escalation, fifty-nine patients (64.8%) were successful in increasing IFXTL ≥5 ug/ml within subsequent infusions. These patients presented higher rates of clinical remission (79.7% vs 37.5%, P<0.001), and lower rates of treatment discontinuation (20.3% vs 65.6%, P<0.001), surgery (1.7% vs 12.5, P=0.05), and any unfavorable outcome (28.8% vs 68.8%, P<0.001), with a non-significant trend for higher rates of Fc remission (63.8% vs 50%, P=0.147). These patients also presented similar outcomes compared to patients with adequate week 14 IFXTL in respect to clinical remission (P=0.134), Fc remission (P=0.049), hospitalization (P=0.131), surgery (P=0.396), treatment discontinuation (P=0.426), and any unfavorable outcome (P=0.189). Conclusion IFXTL significantly influence early and long-term treatment outcomes. In patients with inadequate IFXTL at week 14, proactive TDM was associated with improved clinical outcomes.