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1.
Vaccine ; 41(26): 3862-3871, 2023 06 13.
Article in English | MEDLINE | ID: covidwho-2313151

ABSTRACT

BACKGROUND: Immunosuppressive therapy used in the treatment of inflammatory bowel disease (IBD) is known to reduce vaccine immunogenicity. AIMS: This study aimed to 1) predict the humoral response elicited by SARS-CoV-2 vaccination in IBD patients based on their ongoing treatment and other relevant patient and vaccine characteristics and 2) assess the humoral response to a booster dose of mRNA vaccine. METHODS: We conducted a prospective study in adult IBD patients. Anti-spike (S) IgG antibodies were measured after initial vaccination and again after one booster dose. A multiple linear regression model was created to predict anti-S antibody titer following initial complete vaccination in different therapeutic groups (no immunosuppression, anti-TNF, immunomodulators and combination therapy). A two-tailed Wilcoxon test for two dependent groups was performed to compare anti-S values before and after the booster dose. RESULTS: Our study included 198 IBD patients. The multiple linear regression identified anti-TNF and combination therapy (versus no immunosuppression), current smoking, viral vector (versus mRNA) vaccine and interval between vaccination and anti-S measurement as statistically significant predictors of the log anti-S antibody levels (p < 0.001). No statistically significant differences were found between no immunosuppression and immunomodulators (p = 0.349) and between anti-TNF and combination therapy (p = 0.997). Statistically significant differences for anti-S antibody titer before and after the booster dose of mRNA SARS-CoV-2 vaccine were found, both for non-anti-TNF and anti-TNF groups. CONCLUSIONS: Anti-TNF treatment (either alone or in combination therapy) is associated with lower anti-S antibody levels. Booster mRNA doses seem to increase anti-S both in non-anti-TNF and anti-TNF treated patients. Special attention should be paid to this group of patients when planning vaccination schemes.


Subject(s)
COVID-19 Vaccines , COVID-19 , Inflammatory Bowel Diseases , Adult , Humans , Adjuvants, Immunologic , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Immunoglobulin G , Inflammatory Bowel Diseases/drug therapy , Necrosis , Prospective Studies , SARS-CoV-2 , Vaccination , Tumor Necrosis Factor Inhibitors/adverse effects
2.
Expert Opin Biol Ther ; 23(3): 293-304, 2023 03.
Article in English | MEDLINE | ID: covidwho-2300215

ABSTRACT

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Humans , Crohn Disease/drug therapy , Colitis, Ulcerative/drug therapy , C-Reactive Protein/analysis , Remission Induction , Italy , Gastrointestinal Agents/therapeutic use , Treatment Outcome , Retrospective Studies , Inflammatory Bowel Diseases/drug therapy
3.
Sci Rep ; 13(1): 7044, 2023 04 29.
Article in English | MEDLINE | ID: covidwho-2299643

ABSTRACT

Patients with inflammatory bowel disease (IBD) treated with biologic and/or immunosuppressant drugs are at increased risk for opportunistic infections. Seroprevalence studies can confirm the diagnosis of SARS-CoV-2 infections as well as the associated risk factors. This is a descriptive study which primary endpoints were to highlight the prevalence of SARS-CoV-2 antibodies in a cohort of IBD patients in March 2021, and to analyze seroconversion in patients with known COVID-19 infection and its relationship with IBD treatments. Patients filled in a questionnaire about symptoms of COVID-19 infection and clinical information about their IBD. All included patients were tested for SARS-CoV-2 antibodies. 392 patients were included. Among patients with clinical infection, 69 patients (17,65%) were IgG-positive, 286 (73,15%) IgG-negative and 36 (9,21%) indeterminate. In relation to seroconversion among patients under biologic treatment, 13 patients of the 23 with a previous positive CRP developed antibodies (56.5%). However, when the influence of immunosuppressive treatment on the probability of developing antibodies was analyzed, no significant differences were seen between those patients with or without treatment (77.8% vs. 77.1%, p = 0.96). In our cohort of IBD patients, after one year of pandemic, there were 18.64% IgG positive patients, a higher prevalence than the general population (15.7%).


Subject(s)
Biological Products , COVID-19 , Inflammatory Bowel Diseases , Humans , COVID-19/epidemiology , Seroepidemiologic Studies , SARS-CoV-2 , Antibodies, Viral , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Immunoglobulin G , Biological Products/therapeutic use
4.
Clin Transl Gastroenterol ; 14(4): e00554, 2023 04 01.
Article in English | MEDLINE | ID: covidwho-2299405

ABSTRACT

INTRODUCTION: There are limited data on the safety profile of the severe acute respiratory syndrome coronavirus-2 vaccine among patients taking immunosuppressive medications. Our aim was to evaluate the adverse events related to the vaccines in a nationwide cohort of patients with inflammatory bowel disease on diverse immunosuppressive medications. METHODS: This was a retrospective cohort study using data from the Veterans Health Administration. The primary outcome was any adverse event of special interest (cerebrovascular accident, venous thromboembolism, acute myocardial infarction, Bell palsy) within 90 days of vaccination. RESULTS: A total of 17,201 patients were included, and 12,351 patients (71.8%) received at least 1 vaccine dose. The most common adverse events were acute myocardial infarction and venous thromboembolism. In inverse probability treatment weighting-adjusted logistic regression, full vaccination was not significantly associated with increased adverse events through 90 days, relative to unvaccinated patients. DISCUSSION: Full severe acute respiratory syndrome coronavirus-2 vaccination was not associated with an increased rate of key adverse events relative to unvaccinated individuals among patients with inflammatory bowel disease.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Myocardial Infarction , Venous Thromboembolism , Humans , COVID-19 Vaccines/adverse effects , Retrospective Studies , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Inflammatory Bowel Diseases/drug therapy
5.
United European Gastroenterol J ; 11(2): 179-188, 2023 03.
Article in English | MEDLINE | ID: covidwho-2295847

ABSTRACT

BACKGROUND: Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). OBJECTIVE: The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. METHODS: We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, C-reactive protein (CRP), faecal calprotectin (FC), IFX trough/antibody levels, and drug survival. RESULTS: 297 patients (CD n = 196 [66%], ulcerative colitis/inflammatory bowel disease unclassified n = 101, [34%]) were switched (followed-up: 7.5 months [6.8-8.1]). This was the third, second and first IFX switch for 67/297 (22.5%), 138/297 (46.5%) and 92/297 (31%) of the cohort respectively. 90.6% of patients remained on IFX during follow-up. The number of switches was not independently associated with IFX persistence after adjusting for confounders. Clinical (p = 0.77), biochemical (CRP ≤5 mg/ml; p = 0.75) and faecal biomarker (FC<250 µg/g; p = 0.63) remission were comparable at baseline, week 12 and week 24. CONCLUSION: Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.


Subject(s)
Biosimilar Pharmaceuticals , Inflammatory Bowel Diseases , Adult , Humans , Infliximab/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Prospective Studies , Cohort Studies , Gastrointestinal Agents/adverse effects , Drug Substitution , Inflammatory Bowel Diseases/drug therapy , C-Reactive Protein/analysis , Leukocyte L1 Antigen Complex
6.
Eur J Gastroenterol Hepatol ; 35(6): 629-634, 2023 Jun 01.
Article in English | MEDLINE | ID: covidwho-2302058

ABSTRACT

BACKGROUND AND AIMS: The purpose of this study was to present data on the safety of anti- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in a cohort of inflammatory bowel disease (IBD) patients of an ongoing multicenter study (ESCAPE-IBD) sponsored by the Italian Group for the study of Inflammatory Bowel Disease (ClinicalTrials.gov Identifier: NCT04769258). METHODS: Anti-SARS-CoV-2 vaccination was administrated to 809 IBD patients. Interviews were conducted to report adverse events related to vaccination. Of these 809, 346 patients were surveyed on the pandemic burden and the main reason for hesitancy in coronavirus disease 2019 vaccination. The chi-square test was used to compare categorical variables. Logistic regression was used to assess the relationship between disease-related characteristics and the onset of adverse events. RESULTS: About 45% of patients had at least one side effect, following the first dose (10%), the second (15%), and both doses (19%). All the adverse events were mild and lasted only a few days. Logistic regression analysis revealed that female sex ( P  < 0.001), younger age ( P  = 0.001), seroconversion ( P  = 0.002), and comorbidity ( P  < 0.001) were significantly associated with adverse events. The survey showed that the main concerns were the possibility of adverse event (33%). Almost all patients (99%) felt safer having been vaccinated at their IBD reference center. CONCLUSION: The vaccine reactions experienced in IBD patients were mostly self-limited. We found high acceptance and good safety of SARS-CoV-2 vaccination in our cohort.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Inflammatory Bowel Diseases , Humans , Female , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Pandemics , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Vaccination/adverse effects
7.
Gastroenterol Hepatol ; 45(10): 805-818, 2022 Dec.
Article in English, Spanish | MEDLINE | ID: covidwho-2259091

ABSTRACT

Patients with inflammatory bowel disease (IBD) may require different immunosuppressive treatments throughout their illness. It is essential to assess the immunization status of patients at diagnosis or, if this is not possible, at least before the beginning of immunosuppressive therapy and, subsequently, administering the appropriate vaccines. Therefore, the aim of this work is to establish clear and concise recommendations on vaccination in patients with IBD in the different settings of our clinical practice including vaccination in children, during pregnancy, breastfeeding or on trips. This consensus document emphasises the differences between inactivated and attenuated vaccines and the different degrees of immunosuppression and correlates them with the administration of both mandatory and optional vaccines recommended to our patients with IBD. Finally, as a summary, 17 recommendations are established based on the available scientific evidence and expert opinion. A multidisciplinary team with extensive experience in IBD and vaccination, made up of specialists in gastroenterology, paediatrics, nursing and pharmacy, has participated in the preparation of these recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Pregnancy , Female , Humans , Child , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Inflammatory Bowel Diseases/drug therapy , Immunosuppressive Agents/adverse effects , Vaccination , Chronic Disease
8.
Am J Gastroenterol ; 118(4): 664-673, 2023 04 01.
Article in English | MEDLINE | ID: covidwho-2266144

ABSTRACT

INTRODUCTION: With the advent of the Omicron variant, there are concerns about the efficacy of current vaccinations, especially among immunocompromised/immunosuppressed patients. Our aim was to determine the efficacy of the first booster dose against Omicron. METHODS: This was a retrospective cohort study using a well-established inflammatory bowel disease (IBD) cohort in the Veterans Health Administration. We followed patients on baseline IBD medications through the month of January 2022 during the Omicron COVID-19 wave and created adjusted models for vaccination and boosting effectiveness in reducing SARS-CoV-2 infection, hospitalization, and all-cause mortality. RESULTS: A total of 22,756 patients with IBD were included, of whom 34.9% had received a booster dose. During follow-up, 622 patients (2.7%) were diagnosed with SARS-CoV-2 infection. In adjusted models, booster status was associated with a 30% reduced hazard of SARS-CoV-2 infection (hazard ratio 0.70 vs unvaccinated status, 95% confidence interval 0.56-0.88, P = 0.002), translating to 25.05% effectiveness. Boosted status was also significantly associated with reduced COVID-19 hospitalization (hazard ratio 0.35, 95% confidence interval 0.16-0.74, P = 0.006), demonstrating a 65.06% effectiveness in adjusted models. There was no significant association between vaccination status and all-cause mortality in adjusted models. DISCUSSION: The boosted state was associated with a lower risk of SARS-CoV-2 infections and COVID-19-related hospitalization. Efficacy was lower than what has been seen against previous variants and decreased with prolonged duration from the booster. These findings suggest that patients with IBD, especially those who are immunosuppressed, should consider getting a second booster as per Centers for Disease Control and Prevention recommendations.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Veterans , Humans , COVID-19 Vaccines/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Retrospective Studies , Vaccine Efficacy , SARS-CoV-2 , Inflammatory Bowel Diseases/drug therapy
9.
Int J Colorectal Dis ; 38(1): 31, 2023 Feb 09.
Article in English | MEDLINE | ID: covidwho-2237502

ABSTRACT

AIMS: To evaluate the impact of SARS-CoV-2 vaccine on IBD activity. METHODS: Adult IBD patients from five large IBD centers in China were enrolled and followed up for 6 months. Patients were divided into vaccinated and unvaccinated groups according to vaccination status. Demographic and clinical data were collected. RESULTS: A total of 280 individuals (213 UC and 67 CD patients) were enrolled in the study. The unvaccinated and vaccinated groups of UC patients were comparable for basic characteristics, including age (t = - 0.8, p = 0.425), sex (χ2 = 0.980, p = 0.322), course of disease (z = - 0.513, p = 0.608), surgical conditions (χ2 = 1.042, p = 0.838), disease extent (χ2 = 4.853, p = 0.088), or baseline drug therapy (χ2 = 7.784, p = 0.064). In the subgroup of UC patients, there was no association between vaccination and disease activities, according to the medium disease activity scores for two groups: unvaccinated patients having scores (IQR) 1(2.75), 1(2), 1(2), and 1(2) at baseline, 1, 3, and 6 months, respectively, whereas vaccinated patients having scores (IQR) 1(2), 1(2), 1(2), and 1(2). Similar conclusions were also derived in the subgroup of CD patients. There were also no statistically significant differences in age (t = - 1.48, p = 0.144), sex (χ2 = 0.003, p = 0.957), course of disease (z = - 0.074, p = 0.941), surgical conditions (χ2 = 0.613, p = 0.594), localization (χ2 = 6.261, p = 0.199), or baseline drug therapy (χ2 = 5.881, p = 0.114) between 2 groups of CD patients. The medium disease activity scores (IQR) of the unvaccinated group at baseline, 1, 3, and 6 months were 1(4), 1(3), 1(3), and 1(3), respectively, whereas those of vaccinated group were 2.5(3.75), 2.5(3.75), 3(2), and 2(2), respectively. Overall, very few participants in this study described worsening IBD disease activity requiring a change or addition of medication. CONCLUSIONS: SARS-CoV-2 vaccine has no adverse effect on disease activity in IBD population. IBD patients should be recommended to receive SARS-CoV-2 vaccine in time.


Subject(s)
COVID-19 , Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Adult , Chlorocebus aethiops , Animals , Humans , Crohn Disease/drug therapy , Colitis, Ulcerative/drug therapy , COVID-19 Vaccines/therapeutic use , Vero Cells , COVID-19/prevention & control , SARS-CoV-2 , Inflammatory Bowel Diseases/drug therapy , China/epidemiology
10.
Expert Opin Ther Targets ; 26(10): 897-909, 2022 10.
Article in English | MEDLINE | ID: covidwho-2232671

ABSTRACT

INTRODUCTION: The renin-angiotensin system (RAS) is an important homeostatic pathway, with emerging evidence for the impact of its components on inflammation and fibrosis in gastrointestinal tissues. This review aims to review current knowledge of the physiological mechanism of RAS in inflammatory bowel disease (IBD), and potential therapeutic implications. AREAS COVERED: An extensive online literature review including Pubmed, Medline, and Google Scholar was undertaken. Discussion on the components of the RAS, localization, and physiological functions in the gastrointestinal tract, preclinical, and clinical data in IBD, and the relation with SARS-Cov-2 are covered in this review. EXPERT OPINION: RAS inhibition may have a role as anti-fibrotic adjunct therapy. Targeting the local gastrointestinal RAS with novel modes of delivery may be a target for future therapeutics for IBD, given the widespread availability and safety of current options as utilized in other diseases. Further insight into the mechanism and downstream effects of gastrointestinal ACE2 may lead to a better understanding of the pathogenesis of IBD.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Humans , Renin-Angiotensin System , SARS-CoV-2 , Inflammatory Bowel Diseases/drug therapy , Fibrosis
12.
Indian J Gastroenterol ; 42(1): 70-78, 2023 02.
Article in English | MEDLINE | ID: covidwho-2231646

ABSTRACT

BACKGROUND: The information on seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients with inflammatory bowel disease (IBD) and its comparison to healthy controls is sparse. We compared the seroprevalence rates in patients with IBD and healthy controls (HCs). METHODS: Patients with IBD and HCs (contact of patients) underwent SARS-CoV-2 antibody testing (chemiluminescent immunoassay: Siemens kit IgG against antigen-S1RBD) between July 2020 and April 2021. Information on demography, disease characteristics, drug history and past history of SARS-CoV-2 infection were noted. Patients on 5-aminosalicylic acid or no treatment were considered not on immunosuppressants and those who had received steroids, thiopurines or methotrexate within six months of inclusion were considered being on immunosuppressants. RESULTS: A total of 235 patients (51.9%, males; mean age, 38.7 ± 12.4 years; median disease duration, 60 months [interquartile range, IQR: 36-120]) (ulcerative colitis [UC]: 69.4%, Crohn's disease [CD]: 28.9%, IBD unclassified [IBDU]: 1.7%) and 73 HCs (mean age, 39.6 ± 10.9 years, 80% males) were enrolled. Of the 235 patients, 128 (54.5%) patients were on immunosuppressants and 107 (45.5%) were not on immunosuppressants. Seventy-four (31.5%) patients were seropositive, of which two (0.9%) had previous history of SARS-CoV-2 infection and none received coronavirus disease-19 (COVID-19) vaccine. Seroprevalence between IBD patients and HCs (32% vs. 27%, p > 0.05) and between patients with and without immunosuppressants (28.1% vs. 36%, p > 0.05) was similar. Age, gender, disease type, duration and activity in the last six months; and medication use were similar between patients with positive and negative serology. There was a progressive increase in seroprevalence from July 2020 to April 2021. CONCLUSION: Up to 1/3rd of patients with IBD were seropositive for immunoglobulin G (IgG) SARS-Cov-2 antibody indicating high seroprevalence in patients with IBD from Northern India.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Male , Humans , Adult , Middle Aged , Infant , Female , SARS-CoV-2 , Seroepidemiologic Studies , COVID-19/epidemiology , COVID-19/prevention & control , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Immunosuppressive Agents/therapeutic use , Antibodies, Viral , Immunoglobulin G
13.
Nutrients ; 15(1)2022 Dec 29.
Article in English | MEDLINE | ID: covidwho-2229363

ABSTRACT

The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Adult , Humans , COVID-19/epidemiology , Vitamin D/therapeutic use , SARS-CoV-2 , Pandemics , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Vitamins/therapeutic use , Dietary Supplements
14.
Aliment Pharmacol Ther ; 55(6): 658-669, 2022 03.
Article in English | MEDLINE | ID: covidwho-2223252

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
15.
Lancet Gastroenterol Hepatol ; 8(2): 145-156, 2023 02.
Article in English | MEDLINE | ID: covidwho-2211788

ABSTRACT

BACKGROUND: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. METHODS: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. FINDINGS: Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p<0·0001), BA.1 (107·3 [86·40-133·2] vs 648·9 [523·5-804·5]; p<0·0001), and BA.4/5 (40·63 [31·99-51·60] vs 223·0 [183·1-271·4]; p<0·0001) variants. Breakthrough infection was significantly more frequent in patients treated with infliximab (119 [13·7%; 95% CI 11·5-16·2] of 871) than in those treated with vedolizumab (29 [7·0% [4·8-10·0] of 417; p=0·00040). Cox proportional hazards models of time to breakthrough infection after the third dose of vaccine showed infliximab treatment to be associated with a higher hazard risk than treatment with vedolizumab (hazard ratio [HR] 1·71 [95% CI 1·08-2·71]; p=0·022). Among participants who had a breakthrough infection, we found that higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and, hence, a longer time to breakthrough infection (HR 0·87 [0·79-0·95]; p=0·0028). INTERPRETATION: Our findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies. FUNDING: Royal Devon University Healthcare NHS Foundation Trust; Hull University Teaching Hospital NHS Trust; NIHR Imperial Biomedical Research Centre; Crohn's and Colitis UK; Guts UK; National Core Studies Immunity Programme, UK Research and Innovation; and unrestricted educational grants from F Hoffmann-La Roche, Biogen, Celltrion Healthcare, Takeda, and Galapagos.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Humans , Female , Male , Middle Aged , COVID-19 Vaccines , SARS-CoV-2 , Infliximab/therapeutic use , COVID-19/prevention & control , Prospective Studies , Tumor Necrosis Factor Inhibitors/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Antibodies, Neutralizing , Breakthrough Infections
16.
Int Immunopharmacol ; 116: 109597, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2210529

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. Crohn's disease (CD) and Ulcerative colitis (UC) are the two major types affecting millions across the globe. Various immunomodulatory drugs consisting of small molecules (thiopurines, methotrexate and tofacitinib) and biologics are used to treat IBD. Thiopurines (TP) are widely used in the treatment of IBD and it plays an important role both alone and in combination with anti-TNF agents as IBD maintenance therapy. Although the advent of biologics therapy has significantly advanced the management of IBD, TP remains the mainstay of treatment in resource-limited and low economic settings. However, the recently commenced pandemic has raised uncertainty over the safety of the use of immunosuppressant drugs such as TP among healthcare care providers and patients, as there is a scarcity of data on whether IBD patients are at higher risk of COVID-19 infection or more prone to its severe outcomes. AIM: This review aims to encapsulate evidence on the risk of COVID-19 infection and its severe prognosis in IBD patients on TP. Additionally, it also evaluates the role of TP in inhibiting the viral protease, a potential drug target, essential for the replication and pathogenesis of the virus. CONCLUSION: Emerging evidence suggests that TP therapy is safe during the current pandemic and does not carry an elevated risk when used as monotherapy or in combination with other IBD drugs. In-vitro studies demonstrate that TP is a potential therapeutic for present and future betacoronavirus pandemics.


Subject(s)
COVID-19 , Crohn Disease , Inflammatory Bowel Diseases , Humans , Pandemics , Tumor Necrosis Factor Inhibitors/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Crohn Disease/drug therapy
17.
PLoS One ; 17(8): e0271299, 2022.
Article in English | MEDLINE | ID: covidwho-2196938

ABSTRACT

OBJECTIVE: The adalimumab biosimilars FKB327 and GP2017 were approved for the therapy of patients with inflammatory bowel disease (IBD). Relatively few prospective studies with biosimilar adalimumab in patients with IBD have been published. The aim of this prospective observational study was to evaluate the effectiveness and safety of the biosimilar adalimumab. MATERIAL AND METHODS: Adalimumab biosimilars FKB327 (Hulio®) and GP2017 (Hyrimoz®) were indicated to 50 naive patients in terms of biological therapy with Crohn's disease (CD) or ulcerative colitis (UC). Effectiveness of therapy was evaluated via the Crohn's Disease Activity Index [CDAI] or the Mayo Scoring System [MSS] in patients with CD or UC, respectively, before and after 12 weeks. Additional goals were to evaluate weight changes, laboratory tests and complications or adverse events of this therapy. RESULTS: In CD patients, remission (CDAI <150) was achieved in 73.5% of cases, partial response (≥70-point decrease in CDAI score from baseline) in 11.8%, no response in 11.8% and 2.9% patients discontinued therapy. In UC patients, remission (total score on partial Mayo index ≤2 points) was achieved only in 18.8% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 43.8%, no response in 25.0% and 12.5% patients discontinued therapy. There were statistically significant improvements in CDAI, MSS, haemoglobin, fecal calprotectin, albumin and CRP serum levels after 12 weeks of therapy. Seven adverse events were identified, three of which resulted in therapy being discontinued. CONCLUSIONS: This prospective observational study proved the effectiveness of the adalimumab biosimilars FKB327 and GP2017 in IBD.


Subject(s)
Biosimilar Pharmaceuticals , Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Adalimumab/adverse effects , Biosimilar Pharmaceuticals/adverse effects , Humans , Inflammatory Bowel Diseases/drug therapy , Prospective Studies , Remission Induction , Treatment Outcome
18.
Int J Environ Res Public Health ; 19(23)2022 11 24.
Article in English | MEDLINE | ID: covidwho-2200242

ABSTRACT

Oral health is closely linked to general health status in the form of a bidirectional relationship [...].


Subject(s)
Inflammatory Bowel Diseases , Oral Health , Humans , Inflammatory Bowel Diseases/drug therapy , Patients
19.
EBioMedicine ; 88: 104430, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2178116

ABSTRACT

BACKGROUND: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. METHODS: Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. FINDINGS: Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R2X 0.25, R2Y 0.26, Q2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response. INTERPRETATION: Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response. FUNDING: JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Humans , COVID-19 Vaccines , Antibody Formation , ChAdOx1 nCoV-19 , BNT162 Vaccine , Infliximab , RNA, Ribosomal, 16S , Tumor Necrosis Factor Inhibitors/therapeutic use , SARS-CoV-2 , Inflammatory Bowel Diseases/drug therapy , Metabolome
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