22 CHANGE IN FECAL CALPROTECTIN AND LACTOFERRIN PREDICT CLINICAL REMISSION FOLLOWING INDUCTION THERAPY WITH INFLIXIMAB IN PEDIATRIC CROHN’S DISEASE (CD)

The fecal biomarkers, calprotectin and lactoferrin are noninvasive biomarkers for mucosal inflammation in IBD. While prior cross-sectional studies showed a correlation between these measures, less is known about the relationship of these measurements with treatment response over time. We aimed to assess the correlation between and utility of fecal calprotectin and lactoferrin on treatment response with infliximab (IFX).

We analyzed fecal calprotectin (FCP) and lactoferrin (LCT) as part of a multicenter, prospective anti-TNF induction cohort. IFX induction between 5-10mg/kg occurred at 0, 2 and 6 weeks. Stool and serum were collected prior to IFX treatment (baseline) and during follow-up. We evaluated FCP, LCT and trough IFX levels prior to the first and at subsequent infusions up to infusion 4. The primary outcome was the correlations between FCP, LCT, and outcomes at maintenance. Clinical outcomes were assessed by the wPCDAI measured at each infusion. Clinical remission was defined as wPCDAI <12.5. Spearman correlation was used to assess the relationship between FCP and LCT. Predictive outcomes were calculated by receiver operating characteristics (ROC) with Youden-J statistic.

Among 57 CD patients, 54 (95%) had FCP and LCT measured at both baseline and infusion 4. There was a strong correlation between calprotectin and lactoferrin with data at all time points (R = 0.82, P < 0.0001). The correlation was even stronger at infusion 4 (R = 0.88, P < 0.0001). A delta score for FCP and LCT was calculated by the proportional change between baseline levels to infusion-4 levels. There was a strong correlation between the FCP delta and LCT delta (R = 0.7, P < 0.0001), suggesting similarities in quantifiable change over time. At Infusion 4, an FCP < 378 μg/g predicted sustained clinical remission between week 14 and 6 months with a sensitivity (sens) of 71% and specificity (spec) of 58% (AUC 0.708; P = 0.01). LCT <20.5 μg/g predicted sustained clinical remission between week 14 and 6 months with a sens of 68% and spec of 45% (AUC 0.627; P = 0.117). FCP < 639 μg/g at infusion 4, had a sens of 75% and spec of 75% for achieving an infusion 4 trough level ≥ 5μg/ml (AUC 0.758; P = 0.005). LCT < 34.2 μg/g had a sens of 69% and spec of 54% (AUC 0.692; P = 0.036) for similar trough levels. FCP < 213.6 μg/g at infusion 4, had a sens of 56% and spec of 88% for achieving a infusion 4 trough level > 8μg/ml (AUC 0.744; P = 0.007). LCT < 6.0 μg/g had a sens of 44% and spec of 92% (AUC 0.675; P=0.05) for similar trough levels.

This study demonstrates that both noninvasive biomarkers can be used to predict sustained clinical remission during IFX therapy. It also provides further evidence for the utilization of fecal calprotectin and lactoferrin as predictors to achieve IFX infusion 4 trough level targets for ≥ 5μg/ml and >8μg/ml.

Figure 1.

ROC of IFX ≥ 5 μg/mL at infusion 4

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Figure 2.

ROC of IFX > 8 μg/mL at infusion 4

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