Viral infections and complications in inflammatory bowel disease

This thesis aimed to clarify the impact of several viral infections, their complications and vaccination responses in patients with inflammatory bowel disease (IBD). The first part focuses on two herpes viruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), that can cause severe opportunistic infections, mostly as a rare complication of the use of immunosuppressants. In the second part we studied the risk of the premalignant condition cervical intraepithelial neoplasia (CIN) and cervical cancer caused by human papillomavirus (HPV) in women with IBD and we aimed to identify risk factors, in particular by studying the exposure to immunosuppressants in detail. The third part describes an uncommon case of a hepatitis E virus (HEV) infection in a patient using the gut-selective biologic agent vedolizumab. In the last part of this thesis, we focused on vaccination responses to influenza vaccination and severe acute respiratory coronavirus 2 (SARS-Cov-2) vaccination in immunocompromised patients with IBD and other immune-mediated inflammatory diseases (IMID)

High immunogenicity to influenza vaccination in crohn’s disease patients treated with ustekinumab

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-v

Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease

Background & Aims: Discontinuation of anti–tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing. Methods: This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3–4) versus complete (Mayo 0/SES-CD 0–2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use. Results: Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6–2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43–7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01–0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months. Conclusions: The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse