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Some studies have shown decreased serological response to vaccination in patients on anti-tumor necrosis factor (TNF) medications. While the large majority of these patients do seroconvert after vaccination, titers have generally been lower and one study showed reduced neutralizing and inhibitory functions. One real-world population-based study compared found no increased infection rate in anti-TNF treated patients, but infection rates were low. The low event rate mandates exploration in longer-term population-based data. We used the epi-Israeli IBD Research Nucleus (IIRN) database to explore the effectiveness of COVID-19 vaccination in IBD patients in Israel.

We included all IBD patients insured in two of the four Israeli HMOs, covering 35% of the population, by validated algorithms, and selected those who received two doses of Pfizer BNT162b2 vaccine. These were matched by date of vaccination ±3 days and demographic variables to non-IBD controls. The primary outcome was incidence of positive COVID-19 PCR following vaccination between December, 2020 to June, 2021.

12,640 IBD patients received two vaccine doses; the matched cohort included 4,946 matched pairs (total 9,892 subjects). Mean age was 50.5±16.1 years and median follow-up was 22 weeks (range 4.1-24.4). Fifteen (0.3%) vaccinated IBD patients tested positive compared with 15 (0.3%) vaccinated non-IBD controls (OR=1 [95%CI 0.49-2.05], p=1.0). Patients on anti-TNF and/or corticosteroids did not have a higher incidence of positivity – neither compared to the entire group nor to IBD patients treated with vedolizumab/ustekinumab, even after precise matching for demographics, underlying diseases and IBD severity.

In a large population-based cohort of IBD patients in Israel, vaccine effectiveness was equivalent to non-IBD controls and was not influenced by treatment with anti-TNF or corticosteroids. Notwithstanding previous findings of impaired serological response in anti-TNF treated IBD patients, this real-world large-scale study shows that vaccine protection is robust in IBD patients, including those on immunosuppressive medications.

Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccine-induced immunity is impacted by commonly used immunosuppressive drug regimens in IBD.

We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) Ab assay, 53-92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15 U/mL, which correlated with 20% viral neutralization).

Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/mL;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/mL;p<0.0001) and uste (561U/mL;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy-treated patients (1020U/mL;p=0.62), nor between controls and vedo-treated patients (944 U/mL;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07-0.14], p<0.0001), tofa (0.36 [95% CI 0.19-0.69],p=0.002) and uste (0.56 [95% CI 0.31-1.00],p=0.049), but not with thiopurine (0.77 [95% CI 0.54-1.11],p=0.17) or vedo (1.01 [95% CI 0.61-1.68],p=0.96). mRNA vaccines (3.67 [95% CI 2.72-4.96],p<0.0001) and older age (0.82 [95% CI 0.73-0.91],p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste.

COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste.  No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual’s immunosuppressive treatment.

Financial support was provided as a Research Grant by Pfizer Ltd.

Educational objectives:
1. To understand the mechanisms of action of hyperbaric oxygen therapy in IBD
2. To review current knowledge regarding the application of hyperbaric oxygen therapy in Crohn's Disease
3. To have an overview of potential areas of focus for future research 

This course has been developed by physicians who had recently participated in the writing of the ECCO Crohn's disease consensus Guidelines. This course is intended for those who are interested in Inflammatory Bowel Disease(s) (IBD). One major aim of this e-learning activity is to increase competence and knowledge with regard to Perianal disease in order to improve patient outcomes.

After this case you will:

• To appreciate the Crohn’s disease natural history
• To appreciate the rationale behind specific treatment decisions
• To understand the right investigations to prescribe to Crohn’s disease patient in specific settings
• To learn appropriate clinical management of Crohn’s disease patients with perianal involvement

Prof Jean-Pierre Hugot describes his team’s work examining associations between contemporary frequency of NOD2 mutations in populations and estimated rates of death from the plague during the medieval period.

https://academic.oup.com/ecco-jcc/pages/podcast

Keywords:

Crohn’s Disease,
Genetic factors.

Current knowledge: What is the problem with FMT therapy?
Complexity of multifactorial diseases complicate simple treatment

1. To consider the factors that affect standards in IBD pathology
2. To explore the availability and content of IBD pathology guidelines and datasets

The lecture outlines some of the factors that influence standards and considers approaches to the improvement of IBD pathology reporting quailty.

Educational objectives:
1. To understand the phylosophy of treatment de-escalation or elective switch
2. To understand in which situation a treatment de-escalation or elective switch can be contemplated
3. To emphasize the clinical results with treatment de-escalation
4. To emphasize the need and methods of disease monitoring and management after de-escalation or elective switch

The phylosphy of treatment de-escalation or elective switch is, after achieving a state of deep remission,  to keep it with the lightest of the best tolerated treatment without jeopardizing disease control. The principle behind this is that the treatment needed once a deep state of remission has been achieved may be substantially different from the one to achieve and initially maintain this remission. Recentent studies have highlighted that not only a sustained steroid-free remission was necessary before such de-escalation, but also the need for enodscopic healing and also normalisation of biomarkers assosiated by biological disease activity. As the disease may relapse any time in up to 50% of the patients over one year and up to 80% over 7-8 years, a regular monitoring is necessary to restore appropriate treatment as soon as possible.

Dr Christopher Cardinale describes his work to uncover the effects of a non-coding SNP on signalling through the JAK2 pathway.