Effectiveness and Safety of Vedolizumab in a Matched Cohort of Elderly and Nonelderly Patients With Inflammatory Bowel Disease


Daniela Pugliese; Giuseppe Privitera; Federica Crispino; Nicolò Mezzina; Fabiana Castiglione; Gionata Fiorino; Lucrezia Laterza; Anna Viola; Lorenzo Bertani; Flavio Caprioli; Maria Cappello; Brigida Barberio; Chiara Ricci; Paola Balestrieri; Marco Daperno; Dario Pluchino; Fernando Rizzello; Maria Lia Scribano; Renato Sablich; Luca Pastorelli; Francesco Manguso; Angela Variola; Antonio Di Sario; Laurino Grossi; Alessandro Armuzzi


Aliment Pharmacol Ther. 2022;56(1):95-109. 

In This Article

Abstract and Introduction


Background: Vedolizumab registration trials were the first to include elderly patients with moderate-to-severe ulcerative colitis (UC) or Crohn's disease (CD), but few real-life data have been reported in this population.

Aims: We investigated the effectiveness and safety of vedolizumab in matched cohorts of elderly and nonelderly UC and CD patients.

Methods: The Long-term Italian Vedolizumab Effectiveness (LIVE) study is a retrospective-prospective study including UC and CD patients who started vedolizumab from April 2016 to June 2017. Elderly patients (≥65 years) were matched clinically 1:2 to nonelderly patients (18–64 years); the 2 groups were followed until drug discontinuation or June 2019.

Results: The study included 198 elderly (108 UC, 90 CD) and 396 matched nonelderly patients (205 UC, 191 CD). Nonelderly UC patients had a significantly higher persistence on vedolizumab compared to elderly patients (67.6% vs. 51.4%, p = 0.02). No significant difference in effectiveness was observed between elderly and nonelderly CD patients (59.4% vs. 52.4%, p = 0.32). Age ≥65 years was associated with lower persistence in UC; for CD, previous exposure to anti-TNF-α agents, Charlson comorbidity index >2 and moderate-to-severe clinical activity at baseline were associated with lower persistence. There were recorded 130 adverse events, with comparable rates between the two groups. A Charlson comorbidity index >2 was associated with an increased risk of adverse events.

Conclusion: Vedolizumab can be considered a safe option in elderly IBD patients. Its effectiveness in elderly UC patients may be reduced, while no age-dependent effect on effectiveness was observed in CD.


Elderly people (age ≥65 years old)[1] represent a significant percentage of patients with inflammatory bowel disease (IBD), accounting for up to 30% of all cases.[2] Elderly IBD patients may be distinguished according to the age when they received the diagnosis (≥65 years vs. <65 years), and elderly-onset IBD has been shown to have unique features and specific challenges.[3,4] Multiple reports showed that elderly IBD patients have a risk of IBD-related surgery comparable[5,6] to or even greater[7,8] than younger patients. This might be partially explained by the underuse of immunosuppressive and biological drugs (mainly anti-tumour necrosis factor [TNF] α), owing to safety concern.[6,7,9]

Thiopurines are commonly avoided in the elderly, due to the increased risk of severe leukopenia or medullary aplasia, opportunistic infections, lymphoma and non-melanoma skin cancer.[10–12] Caution is also recommended with the use of anti-TNF-α drugs, especially when combined with immunomodulators or prednisone, due to an increased risk of opportunistic and severe infections and mortality.[13–15] However, the stratification of risk with immunosuppressive therapy should not solely be based on patients' chronological age; it should also include the assessment of comorbidities and the more comprehensive notion of "frailty", which is defined as the "state in which the ability of older people to cope with everyday or acute stressors is compromised".[16] Recently, a large cohort study of IBD patients found that frailty in the 2 years before treatment with thiopurines or anti-TNF-α agents predicted opportunistic infections during the treatment, even after adjusting for age, comorbidities and concomitant medications.[17]

Patients with moderate-to-severely active Crohn's disease (CD) or ulcerative colitis (UC) who have failed or are intolerant to conventional therapy or anti-TNF-α agents are eligible for vedolizumab, which has been approved by both the US Food and Drug Administration[18] and the European Medicines Agency.[19] Vedolizumab is a fully humanised, monoclonal IgG1k antibody that binds α4β7 integrin expressed on leukocytes and selectively blocks their trafficking to the gut mucosa. Approval was based on results of the GEMINI programme, which were the first clinical trials with biologics that included IBD patients older than 65-years-old, up to 80 years of age; however, elderly patients accounted for only 4% and 2% of the enrolled UC and CD populations, respectively.[20,21] A post hoc analysis of both trials found no significant differences in terms of efficacy and safety when patients were stratified by age into 3 groups.[22] On the basis of this experience, although limited, and considering the drug's gut-selective mechanism of action (supposedly associated with a lower risk of infection), many physicians decide in favour of vedolizumab as the first-line biological therapy for the real-life management of elderly IBD patients.[23]

To date, data on effectiveness and safety of vedolizumab for the treatment of elderly IBD patients are scarce.[24–26] Most of these studies had small sample sizes and did not include matched comparison groups. Therefore, the aim of our study was to compare the effectiveness and safety of vedolizumab between elderly IBD patients (i.e., starting vedolizumab when 65 years old or over) and a matched group of nonelderly IBD patients.