DOP017 Infliximab induction fails to reach targets in Perianal Fistulizing Crohn’s Disease: first results from the ATLANTIC study

Background

In perianal fistulizing Crohn’s Disease (PFCD), higher serum concentrations of infliximab (IFX) have been associated with better outcomes. In clinical practice, the majority of PFCD patients receive dose intensification. However, the pharmacokinetics of IFX treatment in PFCD has not been described specifically. We hypothesized that patients with PFCD have altered IFX pharmacokinetics, compared to Crohn’s disease patients without perianal fistulizing disease (CD).

Methods

Patients with CD and PFCD starting standard dose intravenous IFX (5 mg/kg at week 0,2,6, thereafter every 8 weeks) were enrolled. Pre-infusion samples were collected from the second infusion (week 2) until 26 weeks to measure IFX trough level (TL), and anti-drug antibodies if IFX TL was below 1.0 μg/mL (radioimmunoassay). Target TL during induction were 20 μg/mL at week 2, 15 μg/mL at week 6, and at week 14 10 μg/mL for PFCD and 5.0 μg/mL for CD patients. Statistical analysis included unpaired T-tests and Mann-Whitney U tests for numerical differences, and chi-square tests (X²) for differences in proportions.

Results

A total of 149 patients were included (63 PFCD, 86 CD), and a total of 761 serum samples were analyzed. Patient demographics, including age, disease duration and treatment characteristics were largely comparable between groups, only luminal disease activity and use of concomitant immunomodulators were higher in CD patients (see Table 1).

During induction, target IFX TL were achieved in significantly lower proportion of PFCD compared to CD patients (43% vs. 57%, p=0.038). At week 14, median serum IFX concentrations were significantly lower in PFCD patients (2.8 μg/mL, IQR 1.0-5.4) compared to CD patients (4.8 μg/mL, IQR 2.0–6.6) (p = 0.014) (Figure 1). At week 14, target IFX TL in PFCD patients were achieved in only 9% (5/57) and 46% (36/78) of CD patients (p<0.0001).

Anti-drug antibodies were detected in 16% (10/63) of PFCD patients and 12% (10/86) of CD patients (p=0.169) after a median of 20 weeks (IQR 9-28), which were transient in 35% (7/20) of patients during follow-up.

Conclusion

During induction, standard infliximab dosing results in lower TL in PFCD, compared to CD. The previously suggested target IFX concentration at week 14 is only reached in a fraction of PFCD patients. This may contribute to a prolonged disease burden and may necessitate alternative dosing strategies in PFCD.