High Immunogenicity to Influenza Vaccination in Crohn's Disease Patients Treated with Ustekinumab.

Laura Doornekamp,Marco Goeijenbier,Katharina S Schmitz,Eric C.M Van Gorp,Rogier L Goetgebuer,Ron Fouchier,C Janneke Van Der Woude,Annemarie C De Vries

doi:10.3390/vaccines8030455

Abstract

Influenza vaccination can be less effective in patients treated with immunosuppressive therapy. However, little is known about the effects of ustekinumab; an anti-IL-12/23 agent used to treat Crohn’s disease (CD), on vaccination response. In this prospective study, we assessed immune responses to seasonal influenza vaccination in CD patients treated with ustekinumab compared to CD patients treated with anti-TNFα therapy (adalimumab) and healthy controls. Humoral responses were assessed with hemagglutinin inhibition (HI) assays. Influenza-specific total CD3+, CD3+CD4+, and CD3+CD8+ T-cell responses were measured with flow cytometry. Fifteen patients treated with ustekinumab; 12 with adalimumab and 20 healthy controls were vaccinated for seasonal influenza in September 2018. Seroprotection rates against all vaccine strains in the ustekinumab group were high and comparable to healthy controls. Seroconversion rates were comparable, and for A/H3N2 highest in the ustekinumab group. HI titers were significantly higher in the ustekinumab group and healthy controls than in the adalimumab group for the B/Victoria strain. Post-vaccination T-cell responses in the ustekinumab group were similar to healthy controls. One-month post-vaccination proliferation of CD3+CD8+ T-cells was highest in the ustekinumab group. In conclusion, ustekinumab does not impair immune responses to inactivated influenza vaccination. Therefore, CD patients treated with ustekinumab can be effectively vaccinated for seasonal influenza.

Highlights

Patients with inflammatory bowel disease (IBD) are frequently treated with immunomodulatory or immunosuppressive medication
All adult Crohn’s disease (CD) patients treated with either ustekinumab or adalimumab who wished to receive the seasonal influenza vaccination in September 2018 were asked to participate in the biobank study and were included following written informed consent
This immunomodulatory or immunosuppressive treatment may impair vaccine responses. This prospective cohort study showed that B-cell as well as T-cell responses to inactivated trivalent influenza vaccination (TIV) in patients prospective cohort study showed that B-cell as well as T-cell responses to inactivated TIV in patients with CD during ustekinumab treatment were maintained and not impaired compared to healthy with CD during ustekinumab treatment were maintained and not impaired compared to healthy controls

Summary

Introduction

Patients with inflammatory bowel disease (IBD) are frequently treated with immunomodulatory or immunosuppressive medication. Due to these therapies and the underlying inflammatory disease, they are at risk of more severe complications of infectious diseases [1]. Vaccination against influenza reduces the risk of infection in Vaccines 2020, 8, 455; doi:10.3390/vaccines8030455 www.mdpi.com/journal/vaccines. Influenza vaccination may be less effective in patients treated with immunosuppressive therapies [5,6,7] and immunological mechanisms of the impaired vaccination response in IBD patients are often poorly understood [8]. Immunomodulatory and biologic therapies for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) have become widely available. Adalimumab is a frequently prescribed anti-TNFα agent that is administered subcutaneously and has proven efficacy for CD since

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