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P433 Efficacy of vedolizumab with concomitant corticosteroid or immunomodulator use in patients with ulcerative colitis from GEMINI 1

J.-F. Colombel*1, E.V. Loftus Jr2, C.A. Siegel3, J.D. Lewis4, M. Smyth5, S. Sankoh6, B. Abhyankar7

1Icahn School of Medicine at Mount Sinai Hospital, Gastroenterology, New York, NY, United States, 2Mayo Clinic, Gastroenterology and Hepatology, Rochester, Minnesota, United States, 3Dartmouth-Hitchcock Medical Center, Gastroenterology and Hepatology, Hanover, New Hampshire, United States, 4University of Pennsylvania Perelman School of Medicine, Gastroenterology, Philadelphia, Pennsylvania, United States, 5Takeda Global Research and Development Centre (Europe) Ltd., Medical, London, United Kingdom, 6Takeda Pharmaceuticals International Co., Statistics, Cambridge, Massachusetts, United States, 7Takeda Global Research and Development Centre (Europe) Ltd., Clinical Science, London, United Kingdom

Background

The goals of therapy for ulcerative colitis (UC) include induction of remission, mucosal healing, and maintenance of clinical response. Vedolizumab (VDZ) is a monoclonal antibody to α4β7 integrin with efficacy and safety in patients (pts) with UC. In post hoc analyses of data from the GEMINI 1 trial (NCT00783718),[1] we evaluated the efficacy of VDZ in pts with UC who were receiving stable doses of concomitant corticosteroids (CS), immunomodulators (IMM), or both at baseline and experiencing a flare despite these treatments. The safety of VDZ with CS or IMM in these pts has been presented previously.[2]

Methods

GEMINI 1 consisted of 6 weeks (wks) of induction treatment with double-blind (DB) placebo (PBO) or VDZ (induction intent-to-treat [ITT] population) or open-label (OL) VDZ. VDZ responders at wk 6 were re-randomised in the 46-wk maintenance phase to DB PBO or VDZ every 8 or 4 wks (Q8W or Q4W) (maintenance ITT population). CS use was tapered on or after wk 6 in VDZ responders. In the United States, IMM use was discontinued at study entry for OL VDZ-treated pts and at wk 6 for pts on DB VDZ. Efficacy outcomes in the induction and maintenance ITT populations were stratified by use of CS or IMM or both at baseline of induction (wk 0).

Results

Of the 374 pts randomised to receive DB PBO or VDZ during induction, 37%, 12%, and 20% were taking CS or IMM, or both at baseline. Rates of clinical remission (Figure) and mucosal healing at wks 6 and 52, clinical response at wk 6, and durable clinical response and CS-free clinical remission at wk 52 were numerically higher with VDZ treatment compared with PBO, regardless of concomitant CS and/or IMM use at baseline.

Figure. Percentage of VDZ-treated patients in clinical remission (difference from PBO) at week 6 (end of induction) and (B) week 52 (end of maintenance) by concomitant medication use at week 0 (baseline) in the ITT Populations

ECCOJC jju027 P433 F0001

 

Conclusion

The efficacy of VDZ during GEMINI 1 was similar among pts using CS and/or IMM at baseline and those who were not. The interpretation of data for maintenance treatment is limited by the small sample size and discontinuation of CS and IMM after induction. Because the study was not designed to address outcomes with concomitant medication, conclusions are preliminary, and further explorations of apparent synergy between VDZ and CS or IMM are warranted.

The clinical study was funded by Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.). Medical writing assistance was provided by inVentiv Medical Communications and supported by Takeda Pharmaceuticals International, Inc.

References:

[1] Feagan BG, (2013), Vedolizumab as induction and maintenance therapy for ulcerative colitis, N Engl J Med, 699-710

[2] Colombel JF, (2014), Safety of vedolizumab alone or with concomitant corticosteroids and/or immunosuppressants in patients with ulcerative colitis or Crohn's disease, United European Gastroenterol J, A82