Long-term safety of vedolizumab for inflammatory bowel disease

Abstract

Background: Vedolizumab, a gut-selective α₄ β₇ integrin antibody, is approved for moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD).

Aim: To report the final results from the vedolizumab GEMINI long-term safety (LTS) study.

Methods: The phase 3, open-label GEMINI LTS study (initiated May 2009) enrolled patients with UC or CD from four prior clinical trials and vedolizumab-naïve patients. Vedolizumab LTS was evaluated; efficacy and patient-reported outcomes were exploratory endpoints.

Results: Enrolled patients (UC, n = 894; CD, n = 1349) received vedolizumab 300 mg IV every 4 weeks; median cumulative exposure was 42.4 months (range: 0.03-112.2) for UC and 31.5 months (range: 0.03-100.3) for CD. Over 8 years, adverse events (AEs) occurred in 93% (UC) and 96% (CD) of patients, with UC (36%) and CD (35%) exacerbations most frequent. Serious AEs were reported for 31% (UC) and 41% (CD) of patients. Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients. There were no new trends for infections, malignancies, infusion-related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy. Of the ten deaths (UC, n = 4; CD, n = 6), two were considered drug-related by local investigators (West Nile virus infection-related encephalitis and hepatocellular carcinoma). Continuous vedolizumab maintained clinical response long-term, with 33% (UC) and 28% (CD) of patients in clinical remission at 400 treatment weeks.

Conclusions: The safety profile of vedolizumab remains favourable with no unexpected or new safety concerns. These results further establish the safety of vedolizumab and support its long-term use (NCT00790933/EudraCT 2008-002784-14).

Figure 1

GEMINI LTS patient enrolment. Patients were eligible for enrolment in GEMINI LTS who had completed the Phase 2 long‐term safety study or one of the three Phase 3 GEMINI studies. In addition, a cohort of vedolizumab‐naïve patients were recruited directly into GEMINI LTS. CD, Crohn's disease; HBI, Harvey‐Bradshaw Index; IV, intravenous; LTS, long‐term safety; Q4W, every 4 weeks; UC, ulcerative colitis

Figure 2

Clinical response over time in patients with UC or CD. Clinical response was assessed at baseline, weeks 4, 8, 12 and every 8 weeks thereafter. For patients with UC, clinical response was defined as a decrease in the partial Mayo score of ≥2 points and ≥25% from baseline, with an accompanying decrease in rectal bleeding subscore of ≥1 point from baseline or absolute rectal bleeding subscore of ≤1 point. For patients with CD, clinical response was defined as a ≥3‐point decrease from baseline in the HBI score. Baseline was defined as the last assessment prior to the first dose of study drug administration in GEMINI 1 for patients with UC and GEMINI 2 for patients with CD. For patients who discontinued the study, the final assessed value of clinical response was carried forward to the end of the study. CD, Crohn's disease; HBI, Harvey‐Bradshaw Index; UC, ulcerative colitis

Figure 3

Clinical remission over time in patients with UC or CD. Clinical remission was assessed at baseline, Weeks 4, 8, 12 and every 8 weeks thereafter. For patients with UC, clinical remission was defined as a partial Mayo score of ≤2 with no individual subscore >1. For patients with CD, clinical remission was defined as an HBI score ≤4. For patients who discontinued the study, the final assessed value of clinical response was carried forward to the end of the study. CD, Crohn's disease; HBI, Harvey‐Bradshaw Index; UC, ulcerative colitis

Figure 4

Health‐related quality of life (HRQOL) by indication and assessment tool in patients with UC or CD. HRQOL was assessed at baseline and week 26 and then every 24 weeks for the first 4 years, and yearly from Year 5 onward. Assessments tools included A. IBDQ total score, B. SF‐36 total score, C. EQ‐5D total score, and D. EQ‐5D VAS