P572 Reactive dose escalation of infliximab in patients with Crohn’s disease in TAILORIX leads to improved outcomes

Abstract

Background: In TAILORIX, “proactive” dose escalation based on infliximab (IFX) serum concentrations (TDM groups) had no added value to “reactive” dose escalation based on symptoms (TDM groups and control group).1 We evaluated the performance of reactive dose escalation in terms of restoring IFX exposure and the associated response in patients with Crohn's disease (CD) in TAILORIX Methods: Prospectively collected data from 122 patients in TAILORIX were analysed to explore the effect of reactive dose escalation on IFX trough concentrations (TC), the CD activity index (CDAI), serum CRP, faecal calprotectin (FC) and the CD endoscopic index of severity (CDEIS). Results: A total of 71 dose escalations was performed in 122 patients, of which 37 were reactive, i.e., based on symptoms alone (control group, n = 13) or on a combination of symptoms and biomarkers (TDM groups, n = 24) (Figure 1). IFX TC just before reactive dose escalation (at T0) varied widely (from <0.3 to 23.5 μg/ml) and were <3.0 μg/ml in only 11 of 37 cases. Eight weeks after dose escalation (at T+1), 4 of 11 patients did not achieve an IFX TC ≥3.0 μg/ml. Nevertheless, a significant increase in IFX TC was observed (+2.2[+0.5-+4.7] μg/ml, p = .0001). CDAI dropped from 204[174-292] at T0 to 151[123-224] at T + 1 (p = .002), resulting in restored clinical remission (CDAI <150) in 13 of 26 patients. Median CRP and FC concentrations were not elevated at T0 and were also not found to change after dose escalation (Table 1). Of all pharmacokinetic (PK; IFX TC) and pharmacodynamic (PD; CDAI, CRP and FC) markers at T + 1, an FC <237 μg/g was found to best predict endoscopic remission at Week 54 of therapy (13% misclassification rate). Patients in endoscopic remission at Week 54 (CDEIS < 3) had lower FC at T + 1 compared with patients with endoscopically active disease at Week 54 (p = .035). IFX TC, CDAI and CRP at T0/T + 1 did not differ between patients with/without endoscopically active disease at Week 54. Using regression tree analysis, the strongest PK-PD relation was observed between IFX TC and FC (pooled T0 and T + 1). IFX TC were higher when FC ≤250 μg/g (8.1[4.9-15.1] μg/ml) vs. when FC >250 μg/g (4.4[3.3-7.5] μg/ml) (p = .041). Conclusions: Reactive dose escalation resulted in a clinically relevant drop in CDAI. Higher IFX TC associated with lower FC, which was found to be a predictor of endoscopic remission at Week 54.