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P414 Ustekinumab endoscopic response at Week 16 is associated with early normalisation of faecal calprotectin after induction

R. W. M. Pauwels*1, A. C. de Vries1, J. C. Goet1, N. S. Erler2, C. J. van der Woude1

1Erasmus MC, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands, 2Erasmus MC, Department of Biostatistics, Rotterdam, The Netherlands

Background

Ustekinumab (UST) induction therapy may result in rapid symptom improvement in Crohn’s disease (CD) patients. However, the onset of faecal calprotectin (FC) and endoscopic response during the induction phase is largely unknown. We aimed to assess the onset of effect of UST during the induction phase, based on FC and endoscopy.

Methods

In this single-centre prospective study, patients who were started on UST and had endoscopic inflammation with FC>100 µg/g were included. FC was determined at baseline, Week 2, 4, 8 and 16. Endoscopy was performed at baseline and at Week 16. Endoscopic response was defined as SES-CD reduction ≥50% or Rutgeerts score reduction ≥1. At Week 16 endoscopy, ileum and segmental colon biopsies were collected for histological assessment. Histological severity was scored on a 4-point scale based on pathology reports. Median FC levels at the FU time points and the relative change in FC between baseline and Week 16 were assessed with Wilcoxon Rank-sum test. ROC statistics were used to determine the best FC cut-off and to assess the predictive value.

Results

A total of 38 patients (42% males, median age 39 (28–55) years (IQR)) were included. Thirty-eight/38 patients (100%) received previous anti-TNF therapy, of whom 96% anti-TNF were refractory. In 24/38 patients (63%) UST was combined with corticosteroid induction and completely tapered at Week 16 in 16/24 (67%) patients. Data on histology were available in 23/38 patients. Endoscopic response was observed in 9/38 (24%) and endoscopic remission in 5/38 (13%). Histological remission was observed in 9/23 (39%) patients. Median FC level (µg/g) was 595 at baseline, 488 at Week 2, 447 at Week 4, 401 at Week 8 and 943 at Week 16. Median FC levels at Week 8 (p = 0.012) and 16 (p = 0.020) were significantly lower in patients with endoscopic response (vs. non-responders), see Figure 1. Although not statistically significant, we observed a steep decrease in FC levels from baseline to Week 2 in patients with endoscopic response. For patients with histological remission, no statistical difference in FC was observed. A FC cut-off value of 250 µg/g at Week 8 predicted endoscopic response (AUC=0.75) sensitivity 54%, specificity 82%, PPV 64% and NPV 75%. At Week 16 (AUC=0.77) sensitivity 46%, specificity 95%, PPV 86% and NPV 73%.

Conclusion

Ustekinumab induces as early as Week 2 a steep decrease of FC levels in Crohn’s disease patients with endoscopic response at Week 16. Reliable prediction of endoscopic response trough early serial FC measurements remains challenging in this cohort.

Figure 1. Serial FC measurements in CD patients after the start of ustekinumab.

Median FCP levels (in µg/g) in endoscopic responders: 678 at baseline, 230 at Week 2, 244 at Week 4, 181 at Week 8 and 251 at Week 16. In endoscopic non-responders: 595 (p = 0.69), 643 (p = 0.15), 830 (p = 0.18), 596 (p = 0.012) and 1156 (p = 0.02).