Long-term Safety of Vedolizumab for Inflammatory Bowel Disease

Edward V. Loftus Jr; Brian G. Feagan; Remo Panaccione; Jean-Frédéric Colombel; William J. Sandborn; Bruce E. Sands; Silvio Danese; Geert D'Haens; David T. Rubin; Ira Shafran; Andrejus Parfionovas; Raquel Rogers; Richard A. Lirio; Séverine Vermeire


Aliment Pharmacol Ther. 2020;52(8):1353-1365. 

In This Article

Abstract and Introduction


Background: Vedolizumab, a gut-selective α4β7 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).


Ulcerative colitis (UC) and Crohn's disease (CD) are serious, chronic, idiopathic inflammatory bowel diseases (IBD) characterised by abdominal pain, faecal urgency and diarrhoea with blood and/or mucus.[1,2] In addition to negative effects on health-related quality of life (HRQOL), these progressive diseases can lead to structural bowel damage, loss of function, disability and increase the potential for hospitalisation and surgery. Current treatment strategies typically include a combination of corticosteroids, immunosuppressors and biologic therapies to induce remission. Even with successful initial treatment, patients with UC or CD generally require long-term maintenance therapy.

Vedolizumab is a gut-selective monoclonal antibody directed against α4β7 integrin and approved for the treatment of moderately to severely active UC and CD.[3,4] Previous Phase 3, double-blind, randomised, placebo-controlled studies demonstrated that maintenance treatment with vedolizumab for up to 1 year was effective and well-tolerated in patients with UC (GEMINI 1) or CD (GEMINI 2 and GEMINI 3).[5–7] The GEMINI long-term safety (LTS) study continued assessment of patients treated in the GEMINI studies, in addition to enrolling vedolizumab-naïve patients, with the primary goal of evaluating the LTS of vedolizumab in patients with UC or CD.[8–10] Interim analyses (based on 4 years of follow-up) demonstrated that long-term vedolizumab therapy was well-tolerated and also provided clinical and HRQOL benefits.[8,9] In this final analysis that includes over 2,000 patients, some with over 9 years of follow-up, we report the final safety outcomes, along with exploratory clinical and HRQOL outcomes.