Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system.

Raymond K. Cross,Yongling Xiao,Jingdong Chao,Michael Chiorean,Eric Wu,Francis Vekeman,Anthony W. Wang,Jingjing Qian

doi:10.1371/journal.pone.0225572

Abstract

Vedolizumab is the first gut-selective integrin blocker indicated for patients with Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to examine the adverse events (AEs) profile of vedolizumab compared to anti-tumor necrosis factors (anti-TNFs) indicated for CD and UC using the FDA Adverse Event Reporting System (FAERS) database. AE reports with vedolizumab (5/20/2014–6/30/2015) and CD/UC-indicated anti-TNF drugs (adalimumab, infliximab, certolizumab pegol, and golimumab, during 8/1/1998–6/30/2015) as primary suspects were extracted from the FAERS database. AEs associated with vedolizumab were compared for signals of disproportionate reporting against anti-TNF drugs and all other drugs (1969–6/30/2015), using the proportional reporting ratio (PRR) and the empirical Bayesian geometric mean (EBGM) algorithms. The search retrieved 499 reports for vedolizumab and 119,620 reports for anti-TNFs, with 35.9% and 32.1% of these, respectively, being serious AEs. With the PRR approach, vedolizumab-associated reports had signals for 22 groups of AEs (9 were associated with serious outcomes) relative to anti-TNFs and had 34 signals relative to all other drugs. Signals detected included those reported as warnings in prescribing information and new AEs related to cardiovascular disease. Due to the voluntary nature of FAERS, this finding should be considered hypothesis generating (rather than hypothesis testing). Longer-term observational studies are required to evaluate the safety of vedolizumab.

Highlights

84.7% and 15.3% of all anti-tumor necrosis factor (TNF) reports had an indication for Crohn’s disease (CD) and ulcerative colitis (UC), respectively, and 32.1% were associated with serious outcomes
The safety profile of vedolizumab that has emerged from the analysis of clinical trial data in over 3,000 patients suggests an increased susceptibility to upper respiratory infections, and other serious and opportunistic infections as well as non-specific adverse events (AEs).[9, 49,50,51]
Post-marketing surveillance is currently required for all FDA-approved drugs so that rare AEs or AEs undetected in randomized clinical trials (RCTs) can be detected sooner after use in the real-world clinical setting.[36]

Summary

Introduction

Real-world safety profile of vedolizumab using the US FDA adverse event reporting system (study design, collection, analysis of data) and manuscript preparation, but the interpretation of the results and the decision to submit the final paper were made by each author independently. AbbVie Inc. provided support in the form of salaries for authors [JC, AW], but did not have any additional role in the decision to publish or preparation of the manuscript. Groupe d’analyse provided support in the form of salaries for authors [FV, YX] but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Analysis Group, Inc., provided support in the form of salaries for authors [EW], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section

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Conclusion