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P501. Effects of continued vedolizumab therapy for ulcerative colitis in week 6 induction therapy nonresponders

B. Feagan1, W.J. Sandborn2,3, M. Smyth4, S. Sankoh5, A. Parikh6, I. Fox7, 1Western University/Robarts Research Institute, Robarts Clinical Trials Inc, London, Ontario, Canada, 2University of California, San Diego, Division of Gastroenterology, La Jolla, United States, 3Robarts Clinical Trials Inc., Robarts Research Institute, Western University, London, Ontario, Canada, 4Takeda Development Centre (Europe) Ltd, General Medicine/GI/Renal, London, United Kingdom, 5Takeda Pharmaceuticals International Company, Global Statistics, Cambridge, United States, 6Takeda Pharmaceuticals International, Inc., General Medicine, Deerfield, United States, 7Takeda Pharmaceuticals International Company, Clinical Development, Cambridge, United States

Background

Vedolizumab (VDZ) is a gut-selective, humanized, anti-α4β7 integrin monoclonal antibody that was evaluated for treating ulcerative colitis (UC). In the GEMINI 1 trial, 47.1% of patients had a clinical response to VDZ induction therapy at week (wk) 6. Here the efficacy of continuing VDZ therapy is evaluated in wk 6 nonresponders.

Methods

GEMINI 1 (NCT00783718) patients were randomly assigned to receive placebo (PBO) or VDZ 300 mg (cohort 1) or assigned to receive open-label VDZ (cohort 2) at wks 0 and 2. Those who did not respond to VDZ at wk 6 received open-label VDZ every 4 wks (Q4W) during maintenance, and all PBO-treated patients continued on PBO. Clinical response (reduction in partial Mayo Clinic score [MCS] of ≥2 points and decrease of ≤25%, with a reduction in rectal bleeding subscore of ≥1 point or a rectal bleeding subscore of 0 or 1) and clinical remission (partial MCS of ≤2 points and no subscore >1 point) were assessed in wk 6 nonresponders at wks 10 and 14 (prespecified) and at wk 52 (post hoc). Wk 52 post hoc analyses were also performed for mucosal healing (Mayo Clinic scale endoscopic subscore of 0 or 1) in wk 6 nonresponders and for efficacy end points in wk 6 nonresponders who had clinical response at wk 10 or 14.

Results

At baseline, the median duration of UC in VDZ wk 6 nonresponders (4.6 years) was similar to that of wk 6 responders. Median baseline complete MCS was higher in VDZ wk 6 nonresponders (9.0) than in wk 6 responders (8.0). Rate of previous tumour necrosis factor antagonist failure was higher among wk 6 nonresponders (51%) than among wk 6 responders (32%). Proportions of wk 6 nonresponders who had clinical response, clinical remission, or mucosal healing at wk 10, 14, and 52 were greater with VDZ than with PBO (Table). For both VDZ and PBO, proportions of wk 6 nonresponders who had clinical response, clinical remission, or mucosal healing at wk 52 were similar between those who responded at wk 10 and those who responded at wk 14; small numbers of PBO-treated patients in these subgroups limit this analysis.

Table (abstract P501)
End points inVDZ combined (Induction cohorts 1 and 2)PBO (Induction cohort 1)
Wk 6 Nonresponders aWk 10Wk 14Wk 52Wk 10Wk 14Wk 52
AllWk 10 respondersWk 14 responders AllWk 10 respondersWk 14 responders
n = 322n = 322n = 322n = 102n = 126n = 82n = 82n = 82n = 12n = 17
Clinical response b31.739.128.9515414.620.78.53341
 95% CI(26.6, 36.8)(33.8, 44.5)(23.9, 33.8)(41.3, 60.7)(45.3, 62.7)(7.0, 22.3)(12.0, 29.5)(2.5, 14.6)(6.7, 60.0)(17.8, 64.6)
Clinical remission c11.814.616.134354.99.84.92524
 95% CI(8.5, 15.8)(10.7, 18.5)(12.1, 20.2)(25.1, 43.5)(26.6, 43.2)(1.3, 12.0)(3.3, 16.2)(0.2, 9.5)(0.5, 49.5)(3.4, 43.7)
Mucosal healingNCNC23.64544NCNC8.53335
 95% CI (19.0, 28.2)(35.4, 54.8)(35.0, 52.3) (2.5, 14.6)(6.7, 60.0)(12.6, 58.0)
NC, not collected; PBO, placebo; VDZ, vedolizumab.
a Data are shown as percentages of patients.
b At week 52, clinical response was defined as a reduction in complete Mayo Clinic score of ≥3 points and a decrease of ≥30% from the baseline score, with an accompanying reduction in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point.
c At week 52, clinical remission was defined as a complete Mayo Clinic score of ≤2 points and no subscore >1 point.

Conclusion

Among patients with UC who did respond to VDZ induction therapy at wk 6, those who continued on VDZ Q4W had higher rates of clinical response and remission (wks 10, 14, and 52) and of mucosal healing (wk 52) than did those who received PBO.