Vedolizumab in Combination With Corticosteroids for Induction Therapy in Crohn's Disease: A Post Hoc Analysis of GEMINI 2 and 3.

BACKGROUND: Combined therapy with vedolizumab and corticosteroids may improve clinical response or remission in Crohn's disease. The aim of this study is to assess efficacy and safety/tolerability of vedolizumab plus stable doses of corticosteroids at baseline during induction therapy in moderately to severely active Crohn's disease. METHODS: A post hoc exploratory analysis was performed on data from GEMINI 2 (NCT00783692) and GEMINI 3 (NCT01224171), which assessed outcomes following induction therapy over 6- and 10-week periods, respectively. Patients receiving vedolizumab or placebo were stratified by corticosteroid use at baseline. Efficacy endpoints were clinical remission (CR; Crohn's Disease Activity Index [CDAI] score ≤150 points) and enhanced clinical response (ECR; decrease of ≥100 points in CDAI score from baseline), assessed at week 6 (GEMINI 2 and GEMINI 3) and week 10 (GEMINI 3). Safety endpoints included the incidence of adverse events. RESULTS: Vedolizumab plus corticosteroids resulted in higher CR rates than placebo plus corticosteroids at week 6 in GEMINI 2 and at week 6 and week 10 in GEMINI 3. More patients receiving vedolizumab plus corticosteroids achieved CR at week 6 in GEMINI 2 and at week 10 in GEMINI 3 than patients receiving vedolizumab alone. Vedolizumab plus corticosteroids also resulted in significantly higher ECR rates than placebo plus corticosteroids at all timepoints in both studies. More patients receiving vedolizumab plus corticosteroids achieved higher ECR rates at week 6 in GEMINI 2 and at week 10 in GEMINI 3 than patients receiving vedolizumab alone. Adverse event incidence was similar across groups. CONCLUSIONS: Vedolizumab in combination with stable doses of corticosteroids at baseline may improve induction of clinical response or remission in moderately to severely active Crohn's disease. TRIAL REGISTRATION NUMBERS: NCT00783692, NCT01224171.

Sustained Clinical Remission With Vedolizumab in Patients With Moderate-to-Severe Ulcerative Colitis.

BACKGROUND: Sustaining clinical remission is an important treatment goal in moderate-to-severe UC. This post hoc exploratory analysis assessed the long-term efficacy of vedolizumab in the subset of patients with UC in the GEMINI 1 study who were in clinical remission by week 14 after 3 induction doses, administered at weeks 0, 2, and 6. METHODS: Sustained clinical remission (primary endpoint) was evaluated using 2 definitions: (1) a partial Mayo Score (pMS) of ≤2 with no subscore >1 and (2) a rectal bleeding subscore (RBS) of 0 throughout weeks 14, 26, 38, and 52. RESULTS: The proportion of patients in clinical remission at week 14 was significantly higher in patients receiving vedolizumab (n = 620) compared with placebo (n = 149) (pMS: 32.7% vs 20.1% [percentage-point difference (∆) 12.6%; 95% confidence interval [CI], 5.2-20.0]; RBS: 47.3% vs 28.9% [∆18.4%; 95% CI, 10.1-26.7]). Of patients in clinical remission at week 14, a significantly higher proportion of vedolizumab-treated patients achieved sustained clinical remission compared with placebo (pMS: 66.5% vs 26.7%; ∆39.8%; 95% CI, 22.7-56.9; RBS: 56.7% vs 20.9%; ∆35.7%; 95% CI, 22.3-49.1). Findings were consistent in tumor necrosis factor (TNF) antagonist-naive and antagonist-failure patients. CONCLUSION: Compared with placebo, 35%-40% more patients receiving a full induction course of vedolizumab had sustained clinical remission after 52 weeks of therapy. This result was observed irrespective of TNF antagonist treatment history. Clinical remission at week 14 may therefore be a predictor for sustained clinical remission with vedolizumab.