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DOP070 The relationship between vedolizumab drug concentrations at or before week 6 and remission at week 14 in ulcerative colitis patients from GEMINI 1

X. Roblin*1, M.T. Osterman2, S. Glover3, U. Navaneethan4, M. A. Popa5, T. Wyant6, A. James7, K. Lasch5, M. Rosario6

1CHU de Saint-Etienne, Saint-Etienne, France, 2Hospital of the University of Pennsylvania and the Presbyterian Medical Centre of Philadelphia, Philadelphia, Pennsylvania, United States, 3Southeastern Centre for Inflammatory Bowel Diseases/Affiliate Faculty Biomedical Engineering, University of Florida, Gastroenterology, Hepatology, and Nutrition, Gainesville, Florida, United States, 4Centre for Interventional Endoscopy, Florida Hospital, Orlando, Florida, United States, 5Takeda Pharmaceuticals USA, Inc, Deerfield, Illinois, United States, 6Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, United States, 7Takeda Development Centre Europe Ltd, London, United Kingdom

Background

Vedolizumab (VDZ) is a gut-selective alpha4beta7 integrin antagonist for the treatment of ulcerative colitis (UC). The efficacy and safety of VDZ in UC have been demonstrated in the GEMINI 1 study (NCT00783718).1 In this post-hoc analysis of GEMINI 1 data, we investigated whether early VDZ trough levels correlated with subsequent drug efficacy.

Methods

In GEMINI 1, patients received placebo (PBO) or VDZ at weeks 0 and 2. VDZ-treated patients with response at week 6 were randomised to PBO or VDZ every 8 weeks or every 4 weeks. For this post-hoc analysis, we focused on the recommended every 8-week dosing regimen used in clinical practice. VDZ trough concentrations were determined using a sandwich enzyme-linked immunosorbent assay with a lower detection limit of 0.125 µg/mL from blood samples collected before dosing at weeks 2 and 6 and during the week-4 study visit. Clinical remission, defined as a partial Mayo score ≤ 2 points with no individual sub score > 1 point, was determined at week 14, and VDZ trough concentrations were summarised by remission status. Percentages of patients in clinical remission were summarised for patients stratified into quartiles based on their VDZ trough levels at week 2, 4, or 6.

Results

Patients in clinical remission at week 14 had higher median VDZ trough concentrations at weeks 2, 4, and 6 compared with those not in clinical remission.

Figure 1. VDZ trough concentrations at weeks 2, 4 and 6 in patients with and without remission at week 14ab

When stratified by trough concentration, higher trough concentrations at week 6 were accompanied by higher remission rates at week 14. No definitive trends were observed between week 14 remission rates and trough concentrations at week 2 or 4.

Table 1 Remission rates at week 14 in patients according to week 2, 4 or 6 VDZ trough concentrationa

Conclusion

These data show that VDZ trough concentrations at week 6 correlated with clinical remission rates at week 14. Further evaluation is needed to help identify if there is an optimal concentration range at an early point predictive of clinical remission in UC patients.

The clinical study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company, Ltd. Medical writing assistance was provided by inVentiv Medical Communications and supported by Takeda Development Centre Americas, Inc.

References

[1] Feagan BG. Vedolizumab as induction and maintenance therapy for ulcerative colitis, N Engl J Med 2013;699–710.