Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases

Abstract

BACKGROUND & AIMS: There are few real-world data on the safety of vedolizumab for treatment of Crohn's disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice. METHODS: We performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs. RESULTS: Our analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (n [ 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (n [ 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (n [ 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections. CONCLUSION: In a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections

Effects of vedolizumab in Japanese patients with Crohn’s disease: a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses

“…Importantly, there were no cases of PML, a known toxicity with nonspecific a4 integrin inhibition [28]. In a recent retrospective cohort study, the number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used was associated with infections [29]. This study also reported that gastrointestinal infections were observed in the inflammatory bowel disease patients who were treated with vedolizumab (2.4 per 100 patient years of exposure).…”

Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn’s disease

“…The ideal approach to selecting dual biologic regimens remains to be determined. Vedolizumab or ustekinumab may be ideal adjunct therapies in DBT regimens due to their favourable safety profile 12,13,21,22 . For this reason, most patients in our study received vedolizumab, and the most frequently used pairing was with ustekinumab.…”

“…Conversely, newer approved biologic agents for Crohn's disease such as vedolizumab and ustekinumab have not yet demonstrated these risks. Vedolizumab targets the α4β7 integrin receptor to block lymphocyte homing to the intestinal mucosa, and has demonstrated a favourable safety profile in clinical trial 12 and real‐world 13 settings. Ustekinumab inhibits the common p40 subunit of IL‐12 and −23 and is safe and effective in Crohn's disease.…”

“…We hypothesise that vedolizumab may be an optimal therapeutic anchor to dual biologic therapy due to its favourable safety profile, which is attributed to its gut‐specific mechanism. For similar safety considerations, ustekinumab may be a reasonable alternative anchor 12,13,21,22 . We report the largest cohort to date on the preliminary evidence of efficacy and tolerability of DBT in a high‐risk group of patients with refractory Crohn's disease.…”

Predicting Response to Vedolizumab in Inflammatory Bowel Disease

“…For example, no differences were noted with any concomitant therapy in Israeli cohorts or the VICTORY or Cross Penine cohorts (3,(17)(18)(19). Regardless of these results, it is important to remember that the appeal of the relative safety for VDZ is decreased with combination therapy with corticosteroids and/or immunomodulators (20), and there also does not appear to be the same risk of immunogenicity or benefit of increased trough levels with concomitant immunomodulators for VDZ (21,22) (Table 2).…”