Wojtowicz, Abigail M.

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) and is available in subcutaneous (SC) formulation. This analysis assessed the long-term safety outcomes of specific interest to the SC formulation of VDZ. Methods Patients (pts) who participated in VISIBLE 1 or VISIBLE 2 were eligible to enrol in VISIBLE OLE (NCT02620046). In VISIBLE 1, pts with UC were treated with placebo, VDZ SC or VDZ intravenous (IV). In VISIBLE 2, pts with CD were treated with placebo or VDZ SC. In VISIBLE OLE, pts received VDZ SC 108mg every 2 weeks (Q2W) or weekly. Pts received training on SC administration, and most injections were conducted at home by pt or caregiver. Safety of VDZ SC included assessing anti-VDZ antibody (AVA) status and injection site reaction (ISR) adverse events. Blood specimens for AVA assessment were collected 30 minutes before dosing every 16 weeks, at the final dose and the final safety visit 18 weeks after last dose. Data were assessed by treatment pts received during VISIBLE 1 and 2. Results Overall, 288 pts with UC and 458 pts with CD enrolled in VISIBLE OLE. A mean of 91.1 and 74.2 SC injections were completed by pts with UC and CD, respectively, during the OLE. Among pts with UC, the positive AVA rate was higher in pts previously treated with placebo (17.3%) than those treated with VDZ SC (3.4%) or IV (2.6%) (Table 1). The positive AVA rate was also higher among pts with CD previously treated with placebo (11.4%) than with VDZ SC (1.8%). A total of 14/288 pts (4.9%) with UC reported ISRs (Table 2), most of which were mild and none were serious. Two pts developed moderate ISRs; neither required dose modification and both were resolved. Overall, 19/458 pts (4.1%) with CD reported ISRs (Table 2). The majority of ISRs were mild, 2 were moderate and none were severe, and none required dose modification. No direct correlation between AVA status and ISRs was identified, with 11/14 pts (78.6%) with UC and 17/19 pts (89.5%) with CD who reported ISRs being AVA negative. All 5 pts who were AVA positive and reported an ISR had previously received placebo. The highest rate of ISRs were in pts who received placebo in VISIBLE 1 (13.5%). Conclusion No new long-term safety events were identified with the VDZ SC route of administration compared to IV, except for ISRs. A higher proportion of patients who had previously been treated with placebo than those treated with VDZ during VISIBLE 1 and 2 were AVA positive during VISIBLE OLE, supporting a benefit of continued therapy with VDZ SC after IV induction, rather than cessation of treatment for a period of time.

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderate to severe ulcerative colitis (UC) or Crohn’s disease (CD). The subcutaneous (SC) formulation of VDZ was evaluated during the Phase 3 VISIBLE 1 and 2 studies. We report the long-term efficacy among patients (pts) with UC or CD treated with VDZ SC in the VISIBLE open-label extension (OLE) study. Methods Pts with UC or CD in VISIBLE 1/2 could enrol in VISIBLE OLE (NCT02620046). Pts in VISIBLE 1/2 who completed 52 weeks(W) of treatment with VDZ or placebo (randomised completers) and pts without clinical response at W6 who responded at W14 (non-randomised responders) received VDZ SC 108mg every 2W (Q2W) in the OLE. Pts with worsening disease were escalated to QW dosing. Clinical remission (partial Mayo score ≤2, no subscore >1 in UC; HBI score ≤4 in CD) up to W168 was assessed (pts with missing data or escalated to QW dosing were imputed as non-response, irrespective of clinical status). The number of pts who regained clinical response when escalated to QW dosing was also assessed. Results were summarized by prior VISIBLE 1/2 treatment groups. Results Data from 231 pts with UC and 344 pts with CD were included. In pts with UC, baseline OLE clinical remission rates were 55.0%, 91.3% and 77.1% among randomised completers (N=124) previously treated with placebo, VDZ SC and VDZ IV in VISIBLE 1, respectively. At W168, 40.0%, 56.5% and 62.9%, respectively, were in clinical remission on Q2W dosing. In non-randomised responders with UC (N=107), 57.0% were in clinical remission at baseline and 29.9% at W168 (Figure). In pts with CD, baseline OLE clinical remission rates were 60.3% and 62.0% among randomised completers (N=226) previously treated with placebo and VDZ SC in VISIBLE 2. At W168, 32.4% and 37.3% were in clinical remission on Q2W dosing. In non-randomised responders with CD (N=118), 57.6% were in clinical remission at baseline and 27.1% at W168 (Figure). In pts with UC escalated to QW dosing, 22.2% and 38.1% achieved clinical remission and response at W8 after transitioning to QW. Among pts with CD escalated to QW dosing, 38.6% and 53.5% achieved clinical remission and response by W8 after transitioning to QW. Higher rates of remission and response were noted in VDZ completers than non-randomised responders. No new long-term safety signals were noted with VDZ SC vs IV, except for injection site reactions. Conclusion The clinical benefit of VDZ SC was maintained long-term during VISIBLE OLE. A subset of pts who escalated to QW dosing regained response. Findings support VDZ SC as a treatment option for patients with UC or CD who require long-term maintenance therapy.

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). The subcutaneous (SC) formulation of VDZ was evaluated during the Phase 3 VISIBLE 1 and 2 studies. This analysis reports hospitalisations and surgeries among patients (pts) with UC or CD treated with VDZ SC enrolled in the VISIBLE open-label extension (OLE) study. Methods Pts who participated in VISIBLE 1 or VISIBLE 2 were eligible to enrol in VISIBLE OLE (NCT02620046) and received VDZ SC 108mg every 2 weeks (Q2W) or weekly. Patients were grouped according to their scenario in VISIBLE 1/2: Pts who withdrew between week (W) 6 and W52 (Scenario 1); pts who completed 52 weeks of treatment with VDZ or placebo (Scenario 2); pts without a clinical response at W6 but who responded at W14 and were not randomised (Scenario 3). The proportions of patients who experienced UC or CD related hospitalisation and/or surgery during VISIBLE OLE were assessed by scenario and treatment received during VISIBLE 1/2. Results A total of 288 pts with UC and 458 with CD enrolled in the VISIBLE OLE. The mean (min., max.) duration of VDZ exposure during VISIBLE OLE was 1276.7 days (127, 2577 days) among pts with UC and 1110.0 days (127, 2770 days) among pts with CD. The proportions of pts who had a UC or CD related hospitalisation or surgery during VISIBLE OLE are displayed in Table 1. Across all scenarios, a total of 8.3% (24/288) of pts with UC had a related hospitalisation. In total, 3/288 pts (1.0%) with UC (from Scenarios 1 and 3) had a colectomy. No pts with UC from Scenario 2 had a colectomy. Among pts with CD, a total of 13.1% (60/458) had a related hospitalisation. A total of 19 pts (4.1%) with CD had bowel surgery. Higher rates of IBD related hospitalisations and surgeries were observed in Scenario 1, both in pts with UC and with CD. Conclusion Findings from VISIBLE OLE showed that few pts with UC and CD treated with long-term VDZ SC required IBD related hospitalisations over the course of the study. Notably, very few patients with UC or CD required colectomies or bowel surgery.