Long‐term safety of vedolizumab for inflammatory bowel disease

• Published in: Alimentary pharmacology & therapeutics Vol. 52; no. 8; pp. 1353 - 1365
• Main Authors: Loftus, Edward V., Feagan, Brian G., Panaccione, Remo, Colombel, Jean‐Frédéric, Sandborn, William J., Sands, Bruce E., Danese, Silvio, D’Haens, Geert, Rubin, David T., Shafran, Ira, Parfionovas, Andrejus, Rogers, Raquel, Lirio, Richard A., Vermeire, Séverine
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.10.2020; John Wiley and Sons Inc
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Clinical trials; Cohort Studies; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - epidemiology; Crohn Disease - drug therapy; Crohn Disease - epidemiology; Crohn's disease; Drug-Related Side Effects and Adverse Reactions - epidemiology; Efficacy and Safety of Biologics for Crohn's Disease; Encephalitis; Female; Follow-Up Studies; Gastrointestinal Agents - administration & dosage; Gastrointestinal Agents - adverse effects; Hepatocellular carcinoma; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - epidemiology; Intestine; Leukoencephalopathy; Male; Middle Aged; Original Scientific Paper; Patients; Progressive multifocal leukoencephalopathy; Quality of Life; Remission; Safety; Time Factors; Treatment Outcome; Ulcerative colitis; West Nile virus; Young Adult
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.16060

Summary 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).