Rogers, Raquel

INTRODUCTION: Histologic remission is associated with superior long-term clinical outcomes in ulcerative colitis (UC). VARSITY, the first head-to-head comparison of biologic agents in UC (NCT02497469; EudraCT 2015-000939-33), showed superior clinical remission and endoscopic improvement at Week 52 with vedolizumab (VDZ), a gut-selective, humanized, α 4 β 7 integrin monoclonal antibody, vs adalimumab (ADA), a systemic, human, anti-tumor necrosis factor (anti-TNF) monoclonal antibody. 1 Both VDZ and ADA were generally safe and well-tolerated. 1 This analysis compared histologic improvements with VDZ vs ADA in VARSITY. METHODS: Patients with moderately to severely active UC were randomized 1:1 to active VDZ intravenous (IV) infusions (300 mg)/placebo subcutaneous (SC) injections or placebo IV/active ADA SC (160/80/40 mg). Prespecified histologic exploratory endpoints included histologic remission (Geboes score < 2 or Robarts Histopathology Index [RHI] score < 3) and minimal histologic disease activity (Geboes score < 3.2 or RHI score < 5) at Week 14 and Week 52. Histologic remission was also assessed based on previous anti-TNF use. RESULTS: A total of 769 patients received ≥1 dose of VDZ (n = 383) or ADA (n = 386). Median (range) duration of exposure was 477 (127, 630) days for VDZ and 420 (71, 454) days for ADA. Mean (standard deviation) baseline histologic disease activity was similar between groups (Geboes: VDZ, 15.0 [4.92]; ADA, 15.1 [5.03]; RHI: VDZ, 19.5 [8.74]; ADA, 19.6 [8.89]). Histologic remission induced by VDZ at Week 52 was greater than with ADA in the overall (Geboes or RHI), anti-TNF naïve (Geboes or RHI), and anti-TNF failure (RHI only) groups (Table 1). Histologic remission at Week 14 favored VDZ over ADA, with larger differentiation when using RHI (Table 1). VDZ also outperformed ADA in achieving minimal histologic disease activity at Weeks 14 and 52 (Table 1). CONCLUSION: VARSITY showed that use of VDZ, compared with ADA, achieved higher rates of histologic remission and minimal histologic disease activity at Weeks 14 and 52 in patients with moderately to severely active UC. These data support the use of VDZ over ADA in UC.

INTRODUCTION: VARSITY is the first head-to-head trial comparing the efficacy and safety of 2 biologic therapies, vedolizumab (VDZ) and adalimumab (ADA), in patients with moderately to severely active ulcerative colitis (UC). We previously reported significantly higher rates of clinical remission (31.3% vs 22.5%; P = 0.0061) and endoscopic improvement (39.7% vs 27.7%; P = 0.0005) at Week (Wk) 52 with VDZ vs ADA. 1 METHODS: VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-controlled study (NCT02497469; EudraCT 2015-000939-33). Here we report the predefined, exploratory endpoints of early clinical response and clinical remission (defined in the Table 1) within the first 14 wks, as well as durable clinical remission (patients in clinical remission at Wk 14 and Wk 52). RESULTS: A total of 769 patients received ≥1 dose of VDZ (n = 383) or ADA (n = 386). Baseline characteristics were comparable between the 2 groups. A trend for separation in clinical response started to emerge at Wk 6 favoring VDZ vs ADA. Clinical response at Wk 14 favored VDZ vs ADA (257 [67.1%] vs 177 [45.9%]; treatment difference 21.2%). More patients achieved clinical remission at Wk 14 on VDZ vs ADA (102 [26.6%] vs 82 [21.2%]; treatment difference 5.3%). Patients on VDZ achieved higher rates of durable clinical remission (70 [18.3%] vs 46 [11.9%]); laboratory results correlated with these findings. Post hoc analyses showed a larger mean (standard deviation) change of C-reactive protein (CRP) from baseline to Wk 14 (−32.88 [155.77] nmol/L VDZ vs −3.35 [260.81] nmol/L ADA) and to Wk 52 (−50.87 [174.76] nmol/L VDZ vs −37.21 [169.17] nmol/L ADA) in favor of VDZ. Greater mean declines in fecal calprotectin (FCP) levels were seen in patients on VDZ compared with ADA (Wk 14: −1,551.3 [6,236.70] mg/kg VDZ vs −1,167.6 [4,647.67] mg/kg ADA; Wk 52: −2,187.3 [7,440.42] mg/kg VDZ vs −1,846.6 [4,560.55] mg/kg ADA). CONCLUSION: Patients on VDZ had numerically higher rates of both clinical response and clinical remission by Wk 14 compared with ADA. Patients on VDZ also achieved higher rates of durable clinical remission compared with ADA. CRP and FCP results correlated with these findings. These data on early clinical response and clinical remission, as well as durable remission, further support the use of VDZ over ADA in patients with moderately to severely active UC.