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P483 Infliximab but not adalimumab drug levels predict faecal calprotectin response in Inflammatory Bowel Disease patients on dose-intensified anti-TNF therapy

Noack, S.(1);Little, R.(1);Vaz, K.(1);Ward, M.(1);Sparrow, M.(1);

(1)Alfred Health and Monash University, Department of Gastroenterology, Melbourne, Australia

Background

Secondary loss of response (SLOR) to infliximab (IFX) and adalimumab (ADA) is common and dose intensification is effective in a proportion of patients. Drug level targets associated with response as measured by faecal calprotectin (FCP) after anti-TNF intensification have not been well established.

Methods

Retrospective observational study of consecutive adult patients with Crohn’s disease (CD) or ulcerative colitis (UC) with SLOR commenced on dose-intensified IFX (5mg/kg 6 weekly) or ADA (40mg weekly) between May 2013-August 2020. Patients were managed via a protocolised virtual clinic. Trough anti-TNF drug levels and FCP were measured at baseline, and at 6 and 12 months post dose intensification. FCP response was defined as ≤150μg/g. Inter-group and longitudinal comparisons used Mann-Whitney U and Wilcoxon signed-rank tests, respectively. ROC curves evaluated anti-TNF drug levels predictive of FCP response.

Results

Of 78 patients (56% male, median age 40 years), 60 had CD (58% on IFX) and 18 had UC (100% on IFX). There were no significant differences in patient or disease demographics between FCP responders and non-responders at 6 or 12 months. At 6 months, median IFX level and increment in level from baseline were higher in FCP responders than non-responders in both CD and UC (Table 1). At 6 months, achieving an IFX level ≥5.7μg/mL in CD (AUC 0.82, sensitivity 88%, specificity 65%, p=0.012; Figure 1A) and an IFX level ≥5.2μg/mL in UC (AUC 0.89, sensitivity 100%, specificity 73%, p=0.015; Figure 1B) best predicted FCP response. ADA levels at 6 months and both IFX and ADA levels at 12 months were not predictive of FCP response in any cohort.

 FCP≤150μg/gFCP>150μg/gp-valuen
CD IFX levels 6months7.74.50.01125
CD Δ in IFX levels 0-6months5.53.30.03823
UC IFX levels 6months112.70.01316
UC Δ in IFX levels 0-6months8.71.50.02815
CD ADA levels 6months10100.99915
CD Δ in ADA levels 0-6months5.96.60.53514
CD IFX levels 12months8.46.20.11417
CD Δ in IFX levels 0-12months5.74.40.53616
UC IFX levels 12months9.4130.11710
UC Δ in IFX levels 0-12months6.6110.06710
CD ADA levels 12months11120.81414
CD Δ in ADA levels 0-12months7.67.90.93713

Table 1. Median infliximab (IFX) and adalimumab (ADA) levels (μg/mL) and increment according to faecal calprotectin (FCP) response in Crohn’s disease (CD) and ulcerative colitis (UC).



Figure 1: ROC curves of infliximab (IFX) levels and faecal calprotectin (FCP) response in CD (A) and UC (B) patients at 6 months.

Conclusion

After dose-intensified IFX, CD and UC patients achieving FCP response had greater absolute and increment in drug levels than those with elevated FCP. IFX levels ≥5.7μg/mL and ≥5.2μg/mL at 6 months are predictive of FCP response in CD and UC, respectively. ADA levels were not predictive of FCP response.

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