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2.
Infect Dis Rep ; 14(1): 56-62, 2022 Jan 12.
Article in English | MEDLINE | ID: covidwho-1771175

ABSTRACT

There is limited evidence to guide successful treatment of recurrent Campylobacter infection in patients with common variable immunodeficiency (CVID) already managed on regular immunoglobulin therapy. The role of faecal microbiota transplant (FMT) is uncertain. We report a case of recurrent Campylobacter jejuni infection in a patient with CVID treated with repeated FMT with 18 months of symptom resolution prior to relapse.

3.
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
4.
Aliment Pharmacol Ther ; 55(6): 658-669, 2022 03.
Article in English | MEDLINE | ID: covidwho-1672990

ABSTRACT

BACKGROUND: Recruitment rates for Crohn's disease and ulcerative colitis clinical trials continue to decrease annually. The inability to reach recruitment targets and complete trials has serious implications for stakeholders in the inflammatory bowel disease (IBD) community. Action is required to ensure patients with an unmet medical need have access to new therapies to improve the management of their IBD. AIMS: Identify challenges contributing to recruitment decline in IBD clinical trials and propose potential solutions. METHODS: PubMed and Google were used to identify literature, regulatory guidelines and conference proceedings related to IBD clinical trials and related concepts. Data on IBD clinical trials conducted between 1989 and 2020 were extracted from the Trialtrove database. RESULTS: Key aspects that may improve recruitment rates were identified. An increasingly patient-centric approach should be taken to study design including improvements to the readability of key trial documentation and inclusion of patient representatives in trial planning. Placebo is unappealing to patients; approaches including platform trials should be explored to minimise placebo exposure. Non-invasive imaging, biomarkers and novel digital endpoints should continue to be examined to reduce the burden on patients. Reducing the administrative burden associated with trials via the use of electronic signatures, for example, may benefit study sites and investigators. Changes implemented to IBD trials during the COVID-19 pandemic provided examples of how trial conduct can be rapidly and constructively adapted. CONCLUSIONS: To improve recruitment in Crohn's disease and ulcerative colitis trials, the IBD community should address a broad range of issues related to clinical trial conduct.


Subject(s)
COVID-19 , Colitis, Ulcerative , Inflammatory Bowel Diseases , Colitis, Ulcerative/drug therapy , Humans , Inflammatory Bowel Diseases/drug therapy , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2
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
6.
JGH Open ; 6(1): 76-84, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1611245

ABSTRACT

BACKGROUND AND AIM: Patients with chronic diseases are believed to be at increased risk of mental health conditions during the COVID-19 pandemic. We aimed to assess the incidence of psychological morbidity in inflammatory bowel disease (IBD) patients during the COVID-19 pandemic, explore for association with risk of severe COVID-19 and other factors, and establish patients' interest in psychological support. METHODS: A survey including the Patient Health Questionnaire-9, General Anxiety Disorder-7, and Perceived Stress Scale tools for depression, anxiety, and stress was administered to IBD patients from a tertiary center in London, United Kingdom, in June 2020. RESULTS: Two hundred seventy-four patients responded to the survey (57% response rate), with 271 (99%) completing it. Moderate-severe depression was observed in 61 (22.5%), while 49 (18%) had moderate-severe anxiety; 39 (14%) had both diagnoses. Mean (SD) stress score was 16.2 (7.4). There was no association between degree of severe COVID-19 risk and psychological morbidity. Flare symptoms and fatigue were associated with worse psychological morbidity, while accessibility of information regarding COVID-19 risk and reducing that risk was protective for depression (odds ratio [OR] 0.56 [0.33-0.94], P = 0.03), anxiety (OR 0.62 [0.4-0.96], P = 0.03), and stress (standardized ß-coefficient -0.15 [-0.28 to -0.03], P = 0.02). Seventy-nine (30%) respondents were interested in receiving psychological support during the pandemic, while 200 (76%) expressed interest beyond the pandemic. CONCLUSIONS: Although depression, anxiety, and stress among IBD patients during the pandemic were common, their frequency was similar to pre-pandemic rates and recent general population levels. Ensuring easy access to personalized risk information with targeted psychological support may mitigate psychological burden as patients reintegrate into society and deal with future COVID-19 waves.

7.
J Crohns Colitis ; 16(3): 389-397, 2022 Mar 14.
Article in English | MEDLINE | ID: covidwho-1393233

ABSTRACT

BACKGROUND AND AIMS: Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-tumour necrosis factor [anti-TNF] level influences serological responses, remains unknown. METHODS: Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibody responses were measured in surplus serum from 11 422 (53.3% [6084] male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between January 29 and September 30, 2020. Data were linked to nationally held SARS-CoV-2 PCR results to July 11, 2021. RESULTS: Rates of PCR-confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% [178/5893], adalimumab: 3.0% [152/5074], vedolizumab: 6.7% [25/375], p = 0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index [COI] [1.94-9.96] vs 5.02 [2.18-18.70], p = 0.164), but higher in vedolizumab-treated patients (median 21.60 COI [4.39-68.10, p < 0.004). Compared to patients with detectable infliximab and adalimumab drug levels, patients with undetectable drug levels [<0.8 mg/L] were more likely to be seropositive for SARS-CoV-2 antibodies. One-third of patients who had PCR testing prior to antibody testing failed to seroconvert, all were treated with anti-TNF. Subsequent positive PCR-confirmed SARS-CoV-2 was seen in 7.9% [12/152] of patients after a median time of 183.5 days [129.8-235.3], without differences between drugs. CONCLUSION: Anti-TNF treatment is associated with lower SARS-CoV-2 nucleocapsid seroprevalence and antibody reactivity when compared to vedolizumab-treated patients. Higher seropositivity rates in patients with undetectable anti-TNF levels support a causal relationship, although confounding factors, such as combination therapy with a immunomodulator, may have influenced the results.


Subject(s)
Biological Products , COVID-19 , Inflammatory Bowel Diseases , Adalimumab , Adult , Antibody Formation , Biological Products/therapeutic use , Drug Monitoring , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab , Male , SARS-CoV-2 , Seroepidemiologic Studies , Tumor Necrosis Factor Inhibitors/therapeutic use
8.
Gut ; 70(5): 865-875, 2021 05.
Article in English | MEDLINE | ID: covidwho-1388530

ABSTRACT

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2/immunology , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Serologic Tests , United Kingdom/epidemiology
9.
Thorax ; 77(2): 129-135, 2022 02.
Article in English | MEDLINE | ID: covidwho-1247403

ABSTRACT

BACKGROUND: COVID-19 has become the most common cause of acute respiratory distress syndrome (ARDS) worldwide. Features of the pathophysiology and clinical presentation partially distinguish it from 'classical' ARDS. A Research and Development (RAND) analysis gauged the opinion of an expert panel about the management of ARDS with and without COVID-19 as the precipitating cause, using recent UK guidelines as a template. METHODS: An 11-person panel comprising intensive care practitioners rated the appropriateness of ARDS management options at different times during hospital admission, in the presence or absence of, or varying severity of SARS-CoV-2 infection on a scale of 1-9 (where 1-3 is inappropriate, 4-6 is uncertain and 7-9 is appropriate). A summary of the anonymised results was discussed at an online meeting moderated by an expert in RAND methodology. The modified online survey comprising 76 questions, subdivided into investigations (16), non-invasive respiratory support (18), basic intensive care unit management of ARDS (20), management of refractory hypoxaemia (8), pharmacotherapy (7) and anticoagulation (7), was completed again. RESULTS: Disagreement between experts was significant only when addressing the appropriateness of diagnostic bronchoscopy in patients with confirmed or suspected COVID-19. Adherence to existing published guidelines for the management of ARDS for relevant evidence-based interventions was recommended. Responses of the experts to the final survey suggested that the supportive management of ARDS should be the same, regardless of a COVID-19 diagnosis. For patients with ARDS with COVID-19, the panel recommended routine treatment with corticosteroids and a lower threshold for full anticoagulation based on a high index of suspicion for venous thromboembolic disease. CONCLUSION: The expert panel found no reason to deviate from the evidence-based supportive strategies for managing ARDS outlined in recent guidelines.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19 Testing , Humans , Pandemics , Research , Respiration, Artificial , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , United Kingdom/epidemiology
10.
Gut ; 70(10): 1884-1893, 2021 10.
Article in English | MEDLINE | ID: covidwho-1203979

ABSTRACT

OBJECTIVE: Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine. DESIGN: Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4ß7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine. RESULTS: Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine. CONCLUSION: Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Gastrointestinal Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Viral/immunology , Antibody Formation/immunology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Serologic Tests
11.
Gut ; 70(5): 865-875, 2021 05.
Article in English | MEDLINE | ID: covidwho-1146071

ABSTRACT

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2/immunology , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Serologic Tests , United Kingdom/epidemiology
12.
BMJ Open Gastroenterol ; 8(1)2021 02.
Article in English | MEDLINE | ID: covidwho-1088232

ABSTRACT

OBJECTIVE: To evaluate the risk of common infections in individuals with inflammatory bowel disease (IBD) [ulcerative colitis and Crohn's disease] compared with matched controls in a contemporary UK primary care population. DESIGN: Matched cohort analysis (2014-2019) using the Royal College of General Practitioners Research and Surveillance Centre primary care database. Risk of common infections, viral infections and gastrointestinal infections (including a subset of culture-confirmed infections), and predictors of common infections, were evaluated using multivariable Cox proportional hazards models. RESULTS: 18 829 people with IBD were matched to 73 316 controls. People with IBD were more likely to present to primary care with a common infection over the study period (46% vs 37% of controls). Risks of common infections, viral infections and gastrointestinal infections (including stool culture-confirmed infections) were increased for people with ulcerative colitis and Crohn's disease compared with matched controls (HR range 1.12-1.83, all p<0.001). Treatment with oral glucocorticoid therapy, immunotherapies and biologic therapy, but not with aminosalicylates, was associated with increased infection risk in people with IBD. Despite mild lymphopenia and neutropenia being more common in people with IBD (18.4% and 1.9%, respectively) than in controls (6.5% and 1.5%, respectively), these factors were not associated with significantly increased infection risk in people with IBD. CONCLUSION: People with IBD are more likely to present with a wide range of common infections. Health professionals and people with IBD should remain vigilant for infections, particularly when using systemic corticosteroids, immunotherapies or biologic agents. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT03835780).


Subject(s)
Colitis, Ulcerative , Colitis , Inflammatory Bowel Diseases , Cohort Studies , Colitis, Ulcerative/complications , Humans , Inflammatory Bowel Diseases/complications , Primary Health Care
13.
J Crohns Colitis ; 14(12): 1769-1776, 2020 Dec 02.
Article in English | MEDLINE | ID: covidwho-1066288

ABSTRACT

There have been immediate and profound impacts of SARS-CoV-2 and COVID-19 on health care services worldwide, with major consequences for non COVID-19 related health care. Alongside efforts to reconfigure services and enable continued delivery of safe clinical care for patients with IBD, consideration must also be given to management of IBD research activity. In many centres there has been an effective shutdown of IBD clinical trial activity as research sites have switched focus to either COVID-19 related research or clinical care only. As a result, the early termination of trial programmes, and loss of potentially effective therapeutic options for IBD, has become a real and worrying prospect. Moreover, in many countries research activity has become embedded into clinical care-with clinical trials often providing access to new therapies or strategies-which would otherwise not have been available in standard clinical pathways. This pandemic has significant implications for the design, conduct, analysis, and reporting of clinical trials in IBD. In this Viewpoint, we share our experiences from a clinical and academic perspective in the UK, highlighting the early challenges encountered, and consider implications for patients and staff at research sites, sponsors, research ethics committees, funders, and regulators. We also offer potential solutions both for now and for when we enter a recovery phase from the pandemic.


Subject(s)
COVID-19/prevention & control , Clinical Trials as Topic/statistics & numerical data , Health Services Accessibility/trends , Inflammatory Bowel Diseases/therapy , Clinical Trials as Topic/methods , Humans , Patient Selection , Research Design/trends , United Kingdom
14.
GastroHep ; 2(6): 318-326, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-963136

ABSTRACT

BACKGROUND: To quantify the effects of COVID-19 on our inflammatory bowel disease (IBD) unit, including service provision, prescribing practices and use of therapeutic drug monitoring (TDM). METHODS: We performed a single centre retrospective observational cohort study. Data was extracted from our IBD database, electronic patient records and radiology/endoscopy reporting systems between 16/3/20-17/4/20 and the corresponding period in 2019. RESULTS: A similar number of patients commenced biologic therapy before COVID-19 (n = 37) and during the pandemic (n = 36). Patients in the pre-COVID-19 cohort were older (median 36 vs 29 years, P = 0.009) with a longer median disease duration (9.3 vs 5.2 years, P = 0.02). During COVID-19 there was a nonsignificant increase in prescribing of vedolizumab (8/37, 22% vs 14/36, 39%, P = 0.13) and a higher proportion of patients were anti-TNF-naïve (3/17, 18% vs 18/24, 74%, P = 0.0004). There was a reduction in use of concomitant immunomodulators (22/29, 76% vs 4/34, 12%, P < 0.0001) and increased biologic use in thiopurine-naïve patients (3/37, 8% vs 15/36, 42%, P = 0.001). Use of TDM fell by 75% (240 vs 59 tests). Outpatient appointments fell by 68% and were conducted via telemedicine. MRI scanning, endoscopy, luminal surgery and inpatient numbers fell by 87%, 85%, 100% and 82% respectively. IBD Clinical Nurse Specialist and Pharmacist helpline contacts increased by 76% and 228% respectively. CONCLUSIONS: We observed prescribing differences during COVID-19, bypassing the initiation of immunomodulators and/or anti-TNF therapy in favour of vedolizumab with a reduction in immunomodulator prescribing. We also observed a rapid reorganisation of service provision, including a shift towards telemedicine and online solutions.

16.
Gut ; 70(6): 1044-1052, 2021 06.
Article in English | MEDLINE | ID: covidwho-740292

ABSTRACT

OBJECTIVE: Paediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn's and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison. DESIGN: We convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases. Panellists rated the appropriateness of interventions for ASC in the context of the COVID-19 pandemic. Results were discussed at a moderated meeting prior to a second survey. RESULTS: Panellists recommended patients with ASC have a SARS-CoV-2 swab and expedited biological screening on admission and should be isolated. A positive swab should trigger discussion with a COVID-19 specialist. Sigmoidoscopy was recommended prior to escalation to second-line therapy or colectomy. Methylprednisolone was considered appropriate first-line management in all, including those with symptomatic COVID-19. Thromboprophylaxis was also recommended in all. In patients requiring second-line therapy, infliximab was considered appropriate irrespective of SARS-CoV-2 status. Delaying colectomy due to SARS-CoV-2 infection was considered inappropriate. Corticosteroid tapering over 8-10 weeks was deemed appropriate for all. After successful corticosteroid rescue, thiopurine maintenance was rated appropriate in patients with negative SARS-CoV-2 swab and asymptomatic patients with positive swab but uncertain in symptomatic COVID-19. CONCLUSION: Our COVID-19-specific adaptations to paediatric ASC guidelines using a RAND panel generally support existing recommendations, particularly the use of corticosteroids and escalation to infliximab, irrespective of SARS-CoV-2 status. Consideration of routine prophylactic anticoagulation was recommended.


Subject(s)
Anticoagulants/therapeutic use , COVID-19 , Colectomy/methods , Colitis, Ulcerative , Crohn Disease , Infliximab/therapeutic use , Methylprednisolone/therapeutic use , Adolescent , COVID-19/epidemiology , COVID-19/therapy , Child , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/therapy , Crohn Disease/epidemiology , Crohn Disease/therapy , Humans , Immunosuppressive Agents/classification , Immunosuppressive Agents/therapeutic use , Patient Care Management/methods , Patient Care Management/standards , Patient Care Management/trends , Practice Guidelines as Topic , Risk Adjustment/methods , SARS-CoV-2/isolation & purification , Severity of Illness Index , Sigmoidoscopy/methods , United Kingdom
17.
Frontline Gastroenterol ; 11(5): 343-350, 2020.
Article in English | MEDLINE | ID: covidwho-705790

ABSTRACT

OBJECTIVE: To determine the challenges in diagnosis, monitoring, support provision in the management of inflammatory bowel disease (IBD) patients and explore the adaptations of IBD services. METHODS: Internet-based survey by invitation of IBD services across the UK from 8 to 14 April 2020. RESULTS: Respondents from 125 IBD services completed the survey. The number of whole-time equivalent gastroenterologists and IBD nurses providing elective outpatient care decreased significantly between baseline (median 4, IQR 4-7.5 and median 3, IQR 2-4) to the point of survey (median 2, IQR 1-4.8 and median 2, IQR 1-3) in the 6-week period following the onset of the COVID-19 pandemic (p<0.001 for both comparisons). Almost all (94%; 112/119) services reported an increase in IBD helpline activity. Face-to-face clinics were substituted for telephone consultation by 86% and video consultation by 11% of services. A variation in the provision of laboratory faecal calprotectin testing was noted with 27% of services reporting no access to faecal calprotectin, and a further 32% reduced access. There was also significant curtailment of IBD-specific endoscopy and elective surgery. CONCLUSIONS: IBD services in the UK have implemented several adaptive strategies in order to continue to provide safe and high-quality care for patients. National Health Service organisations will need to consider the impact of these changes in current service delivery models and staffing levels when planning exit strategies for post-pandemic IBD care. Careful planning to manage the increased workload and to maintain IBD services is essential to ensure patient safety.

19.
Gut ; 69(10): 1769-1777, 2020 10.
Article in English | MEDLINE | ID: covidwho-591855

ABSTRACT

OBJECTIVE: Management of acute severe UC (ASUC) during the novel COVID-19 pandemic presents significant dilemmas. We aimed to provide COVID-19-specific guidance using current British Society of Gastroenterology (BSG) guidelines as a reference point. DESIGN: We convened a RAND appropriateness panel comprising 14 gastroenterologists and an IBD nurse consultant supplemented by surgical and COVID-19 experts. Panellists rated the appropriateness of interventions for ASUC in the context of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Median scores and disagreement index (DI) were calculated. Results were discussed at a moderated meeting prior to a second survey. RESULTS: Panellists recommended that patients with ASUC should be isolated throughout their hospital stay and should have a SARS-CoV-2 swab performed on admission. Patients with a positive swab should be discussed with COVID-19 specialists. As per BSG guidance, intravenous hydrocortisone was considered appropriate as initial management; only in patients with COVID-19 pneumonia was its use deemed uncertain. In patients requiring rescue therapy, infliximab with continuing steroids was recommended. Delaying colectomy because of COVID-19 was deemed inappropriate. Steroid tapering as per BSG guidance was deemed appropriate for all patients apart from those with COVID-19 pneumonia in whom a 4-6 week taper was preferred. Post-ASUC maintenance therapy was dependent on SARS-CoV-2 status but, in general, biologics were more likely to be deemed appropriate than azathioprine or tofacitinib. Panellists deemed prophylactic anticoagulation postdischarge to be appropriate in patients with a positive SARS-CoV-2 swab. CONCLUSION: We have suggested COVID-19-specific adaptations to the BSG ASUC guideline using a RAND panel.


Subject(s)
Betacoronavirus , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/therapy , Coronavirus Infections/epidemiology , Infection Control/organization & administration , Pneumonia, Viral/epidemiology , Acute Disease , COVID-19 , Colitis, Ulcerative/virology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Gastroenterology , Humans , Pandemics/prevention & control , Patient Selection , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Practice Guidelines as Topic , SARS-CoV-2 , Societies, Medical , United Kingdom
20.
Gut ; 69(6): 984-990, 2020 06.
Article in English | MEDLINE | ID: covidwho-72238

ABSTRACT

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.


Subject(s)
Betacoronavirus , Coronavirus Infections , Inflammatory Bowel Diseases , Pandemics , Pneumonia, Viral , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/therapy , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Risk Assessment , SARS-CoV-2 , United Kingdom
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