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4.
Nat Commun ; 13(1): 1379, 2022 03 16.
Article in English | MEDLINE | ID: covidwho-1747222

ABSTRACT

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Viral Vaccines , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Vaccines , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2 , T-Lymphocytes , Tumor Necrosis Factor Inhibitors
5.
Lancet Gastroenterol Hepatol ; 7(4): 342-352, 2022 04.
Article in English | MEDLINE | ID: covidwho-1665600

ABSTRACT

BACKGROUND: The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs. METHODS: In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing. FINDINGS: Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·7]; p<0·0001), or tofacitinib (429·5 U/mL [3·1]; p=0·0012) compared with controls (1578·3 U/mL [3·7]). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL [4·3]; p=0·74), ustekinumab (582·4 U/mL [4·6]; p=0·11), or vedolizumab (954·0 U/mL [4·1]; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08-0·17; p<0·0001) and tofacitinib (0·43, 0·23-0·81; p=0·0095), but not with ustekinumab (0·69, 0·41-1·19; p=0·18), thiopurines (0·89, 0·64-1·24; p=0·50), or vedolizumab (1·16, 0·74-1·83; p=0·51). mRNA vaccines (3·68, 2·80-4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72-0·87; p<0·0001) with lower antibody concentrations. INTERPRETATION: For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual's treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised. FUNDING: Pfizer.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Adolescent , Adult , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Case-Control Studies , Humans , Inflammatory Bowel Diseases/drug therapy , Prospective Studies , SARS-CoV-2
7.
Gut ; 70(Suppl 4):A100, 2021.
Article in English | ProQuest Central | ID: covidwho-1504897

ABSTRACT

IntroductionImmune checkpoint inhibitors (CPI) have transformed the treatment of many advanced cancers but cause immune related adverse events including enterocolitis (CPI-E). The conventional inflammatory bowel diseases ulcerative colitis (UC) and Crohn’s disease (CD) are associated with unfavourable health-related quality of life (HRQoL) outcomes, but there are currently no data on HRQoL in the setting of CPI-E. This study aimed to investigate HRQoL in CPI-E.MethodsA prospective study was conducted across two London hospital trusts between February-April 2021. UC, CD and CPI-E patient cohorts were recruited from outpatient clinics and the biologic infusion unit. Disease activity was assessed using non-invasive scoring systems: modified-Partial Mayo Score (m-PMS), modified-Harvey Bradshaw Index (m-HBI), Simple Crohn’s and Colitis Activity Index (SCCAI) and Common Terminology Criteria for Adverse Events (CTCAE). HRQoL outcomes were assessed using validated questionnaires: Patient Health Questionnaire-8 (PHQ-8), Generalised Anxiety Disorder-7 (GAD-7), IBD-Questionnaire (IBD-Q) and Multidimensional Assessment of Fatigue (MAF).ResultsSeventy-five patients (33 CD, 21 UC, 21 CPI-E) were recruited. 33 CD patients (100%) and 20 UC patients (95.2%) were receiving biologic therapy. Thirteen CPI-E patients (61.9%) received Anti-PD1/PDL1 monotherapy and (38.1%) received combination anti-PD1 and anti-CTLA-4 therapy. Twenty-four CD patients (72.7%), 11 UC patients (52.4%) and 16 CPI-E patients (76.2%) were shielding due to the COVID-19 pandemic. Using m-PMS, m-HBI, SCCAI and CTCAE, >80% in each of the three cohorts were either classed as being in remission or having mild disease activity. Three CPI-E patients (14.3%) had moderate depression (PHQ-8 ≥10) and a further 9 (42.9%) had mild depression (PHQ-8 score 5-9). Nine CPI-E patients (42.9%) had significant fatigue (MAF score ≥30) and 6 (28.6%) had mild or moderate anxiety (GAD-7 ≥5). There were no significant differences in PHQ-8, GAD-7, IBD-Q and MAF between CPI-E, CD and UC patients, suggesting comparable levels of psychological morbidity in the three groups. Significant correlations were found between CPI-E disease activity and IBD-Q and GAD-7 scores.ConclusionOur study suggests that psychological morbidity in CPI-E is common and comparable to rates in CD and UC, even in the setting of clinical remission. Clinicians should be aware of this complication and take a holistic approach to this patient group.

10.
Lancet Gastroenterol Hepatol ; 6(3): 218-224, 2021 03.
Article in English | MEDLINE | ID: covidwho-1195586

ABSTRACT

SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions. In this position statement endorsed by the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) section and IBD Clinical Research Group, we consider SARS-CoV-2 vaccination strategy in patients with IBD. The risks of SARS-CoV-2 vaccination are anticipated to be very low, and we strongly support SARS-CoV-2 vaccination in patients with IBD. Based on data from previous studies with other vaccines, there are conceptual concerns that protective immune responses to SARS-CoV-2 vaccination may be diminished in some patients with IBD, such as those taking anti-TNF drugs. However, the benefits of vaccination, even in patients treated with anti-TNF drugs, are likely to outweigh these theoretical concerns. Key areas for further research are discussed, including vaccine hesitancy and its effect in the IBD community, the effect of immunosuppression on vaccine efficacy, and the search for predictive biomarkers of vaccine success.


Subject(s)
COVID-19 Vaccines/pharmacology , COVID-19/prevention & control , Inflammatory Bowel Diseases , COVID-19/epidemiology , Disease Transmission, Infectious/prevention & control , Gastroenterology/methods , Gastroenterology/trends , Humans , Immunocompromised Host , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/therapy , SARS-CoV-2 , Societies, Medical , United Kingdom , Vaccination/methods
11.
Therap Adv Gastroenterol ; 13: 1756284820974914, 2020.
Article in English | MEDLINE | ID: covidwho-951814

ABSTRACT

The novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus has spread rapidly across the globe, culminating in major global morbidity and mortality. As such, there has been a rapid escalation in scientific and clinical activity aimed at increasing our comprehension of this virus. This volume of work has led to early insights into risk factors associated with severity of disease, and mechanisms that underpin the virulence and dynamics involved in viral transmission. These insights ultimately may help guide potential therapeutics to reduce the human, economic and social impact of this pandemic. Importantly, the gastrointestinal (GI) tract has emerged as an important organ influencing propensity to, and potentially severity of, COVID-19 infection. Furthermore, the gut microbiome has been linked to a variety of risk factors for COVID-19 infection, and manipulation of the gut microbiome is an attractive potential therapeutic target for a number of diseases. While data profiling the gut microbiome in COVID-19 infection to date are limited, they support the possibility of several routes of interaction between COVID-19, the gut microbiome, angiotensin converting enzyme 2 (ACE-2) expression in the small bowel and colon and gut inflammation. This article will explore the evidence that implicates the gut microbiome as a contributing factor to the pathogenesis, severity and disease course of COVID-19, and speculate about the gut microbiome's capability as a therapeutic avenue against COVID-19. LAY SUMMARY: It has been noted that certain baseline gut profiles of COVID-19 patients are associated with a more severe disease course, and the gut microbiome impacts the disease course of several contributory risk factors to the severity of COVID-19. A protein called ACE-2, which is found in the small intestine among other sites, is a key receptor for COVID-19 virus entry; there is evidence that the gut microbiome influences ACE-2 receptor expression, and hence may play a role in influencing COVID-19 infectivity and disease severity. Furthermore, the gut microbiome plays a significant role in immune regulation, and hence may be pivotal in influencing the immune response to COVID-19. In terms of understanding COVID-19 treatments, the gut microbiome is known to interact with several drug classes being used to target COVID-19 and should be factored into our understanding of how patients respond to treatment. Importantly, our understanding of the role of the gut microbiome in COVID-19 infection remains in its infancy, but future research may potentially aid our mechanistic understanding of viral infection, and new ways in which we might approach treating it.

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