P528 Efficacy of vedolizumab with concomitant corticosteroid or immunomodulator use in patients with Crohn's disease in GEMINI 2
J.-F. Colombel*1, E.V. Loftus Jr2, C.A. Siegel3, J.D. Lewis4, M. Smyth5, J. Xu6, 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., Biostatistics, Cambridge, Massachusetts, United States, 7Takeda Global Research and Development Centre (Europe) Ltd., Clinical Science, London, United Kingdom
Crohn's disease (CD) is often treated with corticosteroids (CS) or immunomodulators (IMM). The efficacy and safety of vedolizumab (VDZ), an anti-α4β7 integrin monoclonal antibody for the treatment of CD, were investigated in the GEMINI 2 trial (NCT00783692). Here, the efficacy of VDZ therapy in subgroups of patients (pts) in GEMINI 2 who were on stable doses of CS or IMM or both at baseline (and experiencing a symptom flare-up) are investigated with post hoc analyses. The safety of concomitant CS or IMM use has been presented previously.
In the 6-week (wk) induction phase of GEMINI 2, pts were treated with double-blind (DB) placebo (PBO) or VDZ (induction intent-to-treat [ITT] population) or open-label (OL) VDZ. VDZ responders were re-randomised to DB PBO or VDZ every 8 or 4 wks (Q8W or Q4W) in the 46-wk maintenance phase (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. Clinical efficacy outcomes for VDZ were evaluated by concomitant medication use at study entry.
At baseline (wk 0), 30%, 17%, and 17% of pts were taking CS, IMM, or CS and IMM, respectively. A trend favouring VDZ was observed for most outcomes. With CS or CS and IMM use at baseline, numerically higher percentages of VDZ-treated pts achieved clinical remission (Figure) and enhanced clinical response at wks 6 and 52 and CS-free remission at wk 52 compared with PBO. However, efficacy endpoints for VDZ-treated pts with concomitant IMM use only did not differ numerically from those on PBO.
The clinical efficacy of VDZ induction or maintenance therapy in GEMINI 2 was similar with or without the use of CS or both CS and IMM at baseline. The interpretation of these data is limited by the small sample size and discontinuation of CS and IMM during maintenance treatment. Because the study was not designed to specifically address outcomes with concomitant medication, conclusions are preliminary. The apparent synergy between VDZ and either CS or IMM needs to be further explored in prospective studies.
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.
 Sandborn WJ, (2013), Vedolizumab as induction and maintenance therapy for Crohn's disease, N Engl J Med, 711-721
 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