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P227 Faecal calprotectin reductions in patients achieving mucosal healing with vedolizumab induction therapy in GEMINI 1

J. D. Lewis*1, W. Reinisch2, B. Bressler3, A. Parikh4, H. Yang5, M. Rosario5, A. Roseth6, S. Danese7, B. G. Feagan8, B. E. Sands9, P. Ginsburg10, T. Dassopoulos11, J. Xu5, T. Wyant5

1University of Pennsylvania Perelman School of Medicine, Gastroenterology, Philadelphia, Pennsylvania, United States, 2Univ. Klinik für Innere Medizin III, Vienna, Austria & McMaster University, Hamilton, Ontario, Canada, 3University of British Columbia, Vancouver, BC, Canada, 4Takeda Pharmaceuticals International, Inc, Deerfield, Illinois, United States, 5Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, United States, 6Lovisenberg Diaconal Hospital, Oslo, Norway, 7IBD Centre, Istituto Clinico Humanitas, Milan, Italy, 8Robarts Research Institute, University of Western Ontario, Clinical Trials, London, Ontario, Canada, 9Icahn School of Medicine at Mount Sinai Hospital, New York, New York, United States, 10Gastroenterology Centre of Connecticut, Hamden, Connecticut, United States, 11Gastroenterology Division, Washington University School of Medicine, St. Louis, Missouri, United States

Background

Mucosal healing is an increasingly important outcome for ulcerative colitis (UC) therapy. Faecal calprotectin (FC) is a biomarker for intestinal inflammation in patients with UC. In the GEMINI 1 study (NCT00783718),1 treatment with the gut-selective alpha4beta7 integrin antagonist vedolizumab (VDZ) resulted in a significantly higher proportion of patients with mucosal healing than treatment with placebo (PBO). In these post hoc analyses, the relationship between mucosal healing and FC was evaluated in patients from the GEMINI 1 induction phase.

Methods

In GEMINI 1, patients with moderately to severely active UC received either double-blind PBO or VDZ or open-label VDZ at weeks 0 and 2. Patients’ stool (~20 g) was collected at baseline (week 0) and week 6. FC levels were determined using the PhiCal quantitative enzyme-linked immunosorbent assay. Mucosal healing (ie, Mayo endoscopic sub-score of ≤1 point) at week 6 was evaluated by treatment group and in patients by quartiles according to their baseline FC values. Reduction from baseline FC at week 6 was measured in patients with and without mucosal healing.

Results

Mucosal healing at week 6 was associated with a reduction in baseline FC of about 75% in all treatment groups. Amongst patients without mucosal healing, a higher decline in FC was observed with VDZ therapy than with PBO.

Figure 1. Percentage of baseline FC level at week 6 by treatment and mucosal healing status

Abbreviations: DB, double-blind; FC, faecal calprotectin; OL, open-label; PBO, placebo; VDZ, vedolizumab. Mucosal healing was defined as a Mayo endoscopic score ≤1 point.

Percentages of patients with mucosal healing were higher with VDZ than with PBO, regardless of baseline FC levels, although the absolute treatment difference was reduced in magnitude amongst patients in the lowest FC quartile.

Table 1 Mucosal healing at week 6 by baseline FC concentration

Conclusion

FC was reduced by approximately 75%, with mucosal healing at week 6. Low baseline FC was associated with higher rates of mucosal healing in PBO-treated patients. Treatment differences between VDZ and PBO for achieving mucosal healing were most apparent in those with baseline FC > 341 μg/g and statistically significant when baseline FC was > 2 127 μg/g.

The clinical studies were funded by Millennium Pharmaceuticals, Inc (d/b/a Takeda Development Centre Americas, Inc). Medical writing assistance was provided by inVentiv Medical Communications and supported by Takeda Development Centre Americas, Inc.

References

[1] Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis, N Engl J Med 2013;369:699–710.