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DOP046 Higher serum concentrations of vedolizumab are associated with superior endoscopic outcomes in Crohn’s disease: data from the LOVE-CD trial

S. Berends1,2*, M. Löwenberg2, F. Baert3, R. Mathôt1, E. Clasquin2, C. Van Der Woude4, F. Hoentjen5, P. Bossuyt6, D. Franchimont7, T. Rispens8,9, A. De Vries9, S. Vermeire10, G. D'Haens2

1Academic Medical Center (AMC), Hospital Pharmacy, Amsterdam, The Netherlands, 2Academic Medical Center (AMC), Gastroenterology and Hepatology, Amsterdam, The Netherlands, 3AZ Delta Roeselare-Menen, Gastroenterology, Roeselare-Menen, Belgium, 4Erasmus University Medical Center, Gastroenterology and Hepatology, Rotterdam, The Netherlands, 5Radboud University Medical Center, Gastroenterology and Hepatology, Nijmegen, The Netherlands, 6Imelda GI Clinical Research Center, Gastroenterology, Bonheiden, Belgium, 7Erasme Hospital, Gastroenterology, Brussels, Belgium, 8Sanquin Research and Landsteiner Laboratory, Immunopathology, Amsterdam, The Netherlands, 9Sanquin Diagnostic Services, Biologicals Lab, Amsterdam, The Netherlands, 10University Hospitals Leuven, Gastroenterology and Hepatology, Leuven, Belgium

Background

Vedolizumab (VDZ) is an anti-α4β7 integrin registered for treatment of moderate to severe Crohn’s disease (CD). Prospective data on mucosal healing in CD and the association with VDZ serum concentrations are lacking. We report a first analysis of the ongoing LOVE-CD trial (NCT02646683).

Methods

Patients with moderate–severe CD based on Crohn’s Disease Activity Index (CDAI) 220–450 and the presence of ulcers at baseline endoscopy received 300 mg VDZ at Week 0, 2, and 6 with additional w10 infusion in the absence of clinical response, followed by 300 mg VDZ every 8w. CDAI, C-reactive protein (CRP) and VDZ concentrations were measured before every infusion. Endoscopies were performed at baseline and w26 and scored with the Simple Endoscopic Score for CD (SES-CD). Clinical remission was defined as CDAI<150, endoscopic remission as SES-CD ≤3 and endoscopic response as SES-CD reduction ≥50% compared with baseline. Quartile analysis was performed in the per protocol population (patients who reached w26 and had two endoscopies).

Results

A total of 110 CD (70% female) patients were included, with median ([interquartile range, IQR]) age 36 years [28–46], median disease duration 12 years [6–16]. All patients had failed conventional therapy and 88% failed prior anti-TNF therapy. Median baseline SES-CD was 11 [7–17], median CDAI 263 [238–313], median CRP: 9 [4-22]. At week 26, 76 patients (69%) were still on VDZ and 74/76 patients underwent w26 endoscopy. Endoscopic response was observed in 43/110 (39%), endoscopic remission in 33/110 patients (30%) and clinical remission in 37/110 patients (34%). Patients with endoscopic response at w26 had higher median VDZ concentrations compared with endoscopic non-responders at w6, 10, 14, and 22 (Table 1). Higher proportions of patients achieved endoscopic remission at w26 with higher VDZ quartiles compared with lower quartiles at w6, 10, and 22 (Figure 1). CRP concentrations were inversely correlated with VDZ concentrations (p-value =.001).

Table 1. Vedolizumab serum concentrations (μg/ml).

Endoscopic reponders week 26 (median [interquartile range])Endoscopic non- responders (median [interquartile range])P-valueWeek 227 [25–33]26 [20–33]0.19Week 631 [24–37]23 [16–34]0.02Week 1031 [26–39]25 [14–31]0.006Week 1426 [14–38]13 [5–30]0.007Week 2215 [11–24] 9 [4–14]0.0003

Figure 1. Vedolizumab quartiles and endoscopic remission at week 26.

Conclusion

This is the first prospective trial showing endoscopic response and remission rates with VDZ in CD. VDZ concentrations were significantly higher in patients with an endoscopic response compared with non-responders. The study was support provided by Takeda.