Association of Infliximab and Vedolizumab Trough Levels with Reported Rates of Adverse Events: A Cross-Sectional Study.

Ido Veisman,Oranit Barzilay,Shomron Ben-Horin,Liora Bruckmayer,Bella Ungar,Uri Kopylov,Rami Eliakim,Ola Haj-Natour

doi:10.3390/jcm10184265

Ido Veisman, Oranit Barzilay + Show 6 more

Open Access

https://doi.org/10.3390/jcm10184265

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Abstract

Infliximab and vedolizumab are effective treatments for inflammatory bowel disease (IBD), although associated with adverse events (AE). While low or non-existent drug levels and positive antidrug antibodies have been associated with therapeutic failure, there is no clear association between higher drug levels and AE. A cross-sectional study consisting of Crohn’s disease (CD) and ulcerative colitis (UC) patients receiving infliximab or vedolizumab at the Sheba Medical Center was performed. Patients completed a questionnaire regarding AEs related to biological therapy. Serum trough levels obtained on the same day were analyzed. Objective measures of outcomes were retrieved from medical records. Questionnaires were completed by infliximab (n = 169) and vedolizumab (n = 88)-treated therapy patients. Higher infliximab levels were only numerically associated with the occurrence of at least one AE (p = 0.08). When excluding fatigue and abdominal pain, higher infliximab levels were statistically associated with the occurrence of at least one AE (p = 0.03). Vedolizumab drug levels > 18 μg/mL were also linked with the occurrence of more AEs. No specific association was observed between the increased levels of either infliximab or vedolizumab and specific AEs (neurological symptoms, upper GI symptoms, infectious complications, and musculoskeletal symptoms). As significant AEs are very rare, additional multi-center studies are required.

Highlights

Over the last two decades, biological therapies have revolutionized treatment paradigms in various chronic inflammatory diseases, including inflammatory bowel disease (IBD)
Among the 169 questionnaires filled by infliximabtreated patients, 84 patients completed the questionnaire once, 35 patients completed the questionnaire twice, and five patients completed the questionnaire three times (i.e., 124 infliximab-treated IBD patients participated in this study)
Regarding the 88 questionnaires completed by vedolizumab-treated patients, 56 completed the questionnaire once, 13 completed the questionnaire twice, and two patients completed the questionnaire three times (i.e., 71 vedolizumab-treated IBD patients participated in this study)

Summary

Introduction

Over the last two decades, biological therapies have revolutionized treatment paradigms in various chronic inflammatory diseases, including IBD. Used biologic agents proven effective in IBD treatment are monoclonal antibodies to tumor necrosis factor alpha (TNF) and anti-integrin agents. While these treatments have been shown to be highly effective in IBD, they are not risk-free. Anti-TNF agents are associated with a wide range of adverse events (AEs), the main ones being the increased risk of infections and potential risk of lymphoma [1]. Vedolizumab is a selective anti-α4β7 integrin agent that affects the gastrointestinal (GI) tract. The effects on other systems cannot be ruled out [2].

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