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1.
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
3.
R I Med J (2013) ; 105(10): 42-47, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2125292

ABSTRACT

Patients with inflammatory bowel disease (IBD) may take medications that affect their immune system, altering their ability to fight infection or making them less responsive to vaccines. Many of these patients were excluded from original studies regarding COVID-19, which creates a challenge for gastroenterologists to use evidence-based medicine to guide their management. We reviewed the available literature regarding patients with IBD and COVID-19 outcomes and response to vaccinations. Of all IBD patients, 0.3-24% acquired COVID-19 infection and 7-67% of those patients required hospitalization. Many studies have analyzed the effects of COVID-19 on patients with IBD. Observational studies suggest most IBD patients are not at higher risk from COVID-19 infection and that the COVID-19 vaccines are safe, effective and recommended. However, patients being treated with a TNF-α inhibitor with an immunomodulator and patients being treated with steroids should be monitored closely and efforts should be made to wean patients off of systemic steroids if possible. Patients treated with these regimens had lower antibody responses to vaccination and were at higher risk of acquiring severe COVID-19 infection. Antibody responses were robust after the second dose of mRNA vaccines with 85-100% of individuals showing seroconversion, albeit with lower levels of antibodies compared to the general population.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Vaccines , Humans , COVID-19 Vaccines , Inflammatory Bowel Diseases/drug therapy , Vaccination
4.
Expert Opin Drug Saf ; 21(10): 1249-1257, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2134364

ABSTRACT

INTRODUCTION: Since Anti-IL-17s availability, concerns about their safety have been raised due to the inhibition of physiological activities that IL-17A plays in the immune response against infections. Ixekizumab is a humanized monoclonal antibody specifically targeting IL-17A approved for the treatment of moderate-to-severe psoriasis. AREAS COVERED: The aim of this review is to evaluate the safety profile of ixekizumab in moderate-to-severe psoriasis patients. A compressive literature review has included articles since March 2022. EXPERT OPINION: In our analysis, most of the reported AEs were mild or moderate and rarely required treatment discontinuation. Among the class-specific AEs to consider during ixekizumab treatment, there are the risk of Candida infections and the risk of IBD, both of which were reported more frequently than placebo or other biologics (etanercept, ustekinumab, and guselkumab). However, the reported candidiasis resulted in mild-to-moderate and easily managed. The risk of IBD (both exacerbation and de novo diagnosis) represents a class effect of IL-17 inhibitors, which should be well evaluated before considering starting ixekizumab treatment. The most common AEs were represented by nasopharyngitis, upper respiratory tract infection, and injection-site reactions. The analyzed studies confirmed the favorable safety profile of ixekizumab even in more recently published studies.


Subject(s)
Dermatologic Agents , Inflammatory Bowel Diseases , Psoriasis , Humans , Interleukin-17 , Psoriasis/drug therapy , Ustekinumab , Inflammatory Bowel Diseases/drug therapy , Treatment Outcome , Severity of Illness Index
5.
Med Sci Monit ; 28: e938243, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2100413

ABSTRACT

BACKGROUND The COVID-19 pandemic affected many people worldwide, including those with chronic diseases. Our objective was to analyze its influence on medical care and the course of inflammatory bowel disease (IBD) in Poland. MATERIAL AND METHODS In 2021, 81 patients in Poland with IBD completed an original anonymous questionnaire about the impact of the COVID-19 pandemic on the course of their disease and mental status. The printed questionnaire was distributed to IBD patients treated at the Gastroenterology Outpatient Clinic of the University Clinical Hospital in Bialystok, and an online questionnaire was sent to patients via social media. Statistical analysis was performed using the chi-squared test, with a significance level of P<0.05. RESULTS The study group consisted of 46 women and 35 men with a mean age of 32.42 years. Fifty-nine patients had ulcerative colitis and 22 had Crohn disease. Patients reported significant deterioration in medication availability (50.62%) and restricted access to gastroenterology outpatient clinics (51.90%) (P<0.05). Of patients who contracted COVID-19, 89.47% did not require hospitalization, 32.10% (26/81) were asymptomatic, mild, or moderate, despite immunosuppressive biological treatment (27.16%, 22/81), or steroids (18.52%, 15/81). Over 50% of respondents stated the pandemic negatively affected their mental state and 30% of them associated that with worsening IBD. CONCLUSIONS During the pandemic, respondents were mainly concerned with difficulties in accessing the gastroenterology clinic and limited drug availability. The pandemic negatively affected patients' mental state. In cases of COVID-19 disease, patients with IBD were mostly asymptomatic and did not require hospitalization, despite therapy affecting the immune system.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Male , Humans , Female , Adult , COVID-19/epidemiology , Pandemics , Quality of Life , Poland/epidemiology , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/drug therapy , Surveys and Questionnaires , Chronic Disease
6.
Int J Colorectal Dis ; 37(11): 2277-2289, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2085359

ABSTRACT

BACKGROUND: Between people with and without inflammatory bowel disease (IBD), there was no statistically significant difference in the probability of contracting the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the risk of adverse outcomes in IBD patients after virus infection remains unclear. METHODS: Eligible studies conducted from January 1, 2020 to March 17, 2022 were obtained by searching PubMed, Embase, and Web of Science. Information was collected in tables from the included studies. Random-effects and fixed-effects models were used as measures for the pooled estimates. All data were estimated by R version 4.1.3. RESULTS: Twenty-four studies were included. The risk ratio (RR) of adverse outcomes in COVID-19 patients with IBD increased by 32% (RR 1.32; 95% CI 1.06-1.66) relative to COVID-19 patients without IBD. The RR of mortality was higher in COVID-19 patients with IBD from Europe (RR 1.72; 95% CI 1.11-2.67) than in those that were not from Europe (RR 1.00; 95% CI 0.79-1.26; χ2 = 4.67; P = 0.03). Patients with ulcerative colitis were at higher risk of adverse outcomes after SARS-CoV-2 infection than patients with Crohn's disease patients (RR1.38; 95% CI 1.27-1.50). The IBD drugs treatment was associated with the risk of adverse outcomes, the pooled odds ratio (OR) of mesalazine (1.79; 95% CI 1.59-2.02), immunomodulators (1.30; 95% CI 1.10-1.53), and anti-TNF (0.47; 95% CI 0.41-0.53) were assessed. CONCLUSION: COVID-19 patients with IBD had an increased risk of adverse outcomes than those without IBD, whereas anti-TNF treatment might reduce the risk.


Subject(s)
COVID-19 , Colitis, Ulcerative , Inflammatory Bowel Diseases , Humans , SARS-CoV-2 , COVID-19/complications , Tumor Necrosis Factor Inhibitors , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Colitis, Ulcerative/drug therapy
8.
Aliment Pharmacol Ther ; 56(10): 1460-1474, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2052261

ABSTRACT

BACKGROUND: The COVID-19 pandemic offered a unique opportunity to understand inflammatory bowel disease (IBD) management during unexpected disruption. This could help to guide practice overall. AIMS: To compare prescribing behaviour for IBD flares and outcomes during the early pandemic with pre-pandemic findings METHODS: We performed an observational cohort study comprising patients who contacted IBD teams for symptomatic flares between March and June 2020 in 60 National Health Service trusts in the United Kingdom. Data were compared with a pre-pandemic cohort after propensity-matching for age and physician global assessment of disease activity. RESULTS: We included 1864 patients in each of the pandemic and pre-pandemic cohorts. The principal findings were reduced systemic corticosteroid prescription during the pandemic in Crohn's disease (prednisolone: pandemic 26.5% vs. 37.1%; p < 0.001) and ulcerative colitis (UC) (prednisolone: pandemic 33.5% vs. 40.7%, p < 0.001), with increases in poorly bioavailable oral corticosteroids in Crohn's (pandemic 15.6% vs. 6.8%; p < 0.001) and UC (pandemic 11.8% vs. 5.2%; p < 0.001). Ustekinumab (Crohn's and UC) and vedolizumab (UC) treatment also significantly increased. Three-month steroid-free remission in each period was similar in Crohn's (pandemic 28.4% vs. 32.1%; p = 0.17) and UC (pandemic 36.4% vs. 40.2%; p = 0.095). Patients experiencing a flare and suspected COVID-19 were more likely to have moderately-to-severely active disease at 3 months than those with a flare alone. CONCLUSIONS: Despite treatment adaptations during the pandemic, steroid-free outcomes were comparable with pre-pandemic levels, although concurrent flare and suspected COVID-19 caused worse outcomes. These findings have implications for IBD management during future pandemics and for standard practice.


Subject(s)
COVID-19 , Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Humans , Pandemics , Ustekinumab , State Medicine , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/complications , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/complications , Crohn Disease/epidemiology , Cohort Studies , Adrenal Cortex Hormones/therapeutic use , Prednisolone
10.
Turk J Gastroenterol ; 33(9): 751-759, 2022 09.
Article in English | MEDLINE | ID: covidwho-2040241

ABSTRACT

BACKGROUND: We aimed to determine the clinical features, predictive factors associated with severe disease, and outcomes of coronavirus disease 2019 in patients with immune-mediated inflammatory diseases and report data on the comparison of coronavirus disease 2019 between patients with inflammatory bowel disease and spondyloarthropathies. METHODS: A total of 101 patients with inflammatory bowel disease and spondyloarthropathies who had confirmed diagnosis of coronavirus disease 2019 were retrospectively analyzed. Demographics, comorbidities, immunosuppressive treatments, and the impact of immunosuppression on negative outcomes were assessed. RESULTS: The median age of the patients was 47 (38-57) years. The most common rheumatologic diagnosis was ankylosing spondylitis (n = 24), psoriatic arthritis (n = 17), and reactive arthritis (n = 1). In the inflammatory bowel disease group, 47 patients had ulcerative colitis, 11 Crohn's disease, and 1 unclassified. The most commonly used treatments were biologics (55%) in the spondyloarthropathies group and aminosalicylates (66.1%) in the inflammatory bowel disease group. Overall, 18.8% of the patients required hospitalization, 5% developed severe complications, and 2% died. There were no significant differences in coronavirus disease 2019-related negative outcomes between spondyloarthropathies and inflammatory bowel disease patients. The median age was higher in the patients who required hospitalization [57 (46-66) vs 47 (38-57) years, P=.008]. Bilateral opacities on chest radiographs were more common in the patients who required hospitalization in the spondyloarthropathies group [88.9% vs 14.3%, P=.016]. Comorbidity was significantly associated with hospitalization in the inflammatory bowel disease group (P ≤ .05). Baseline therapy with biologics or immunosuppressives was not associated with severe coronavirus disease 2019 outcomes. CONCLUSION: Older age, comorbidities, and bilateral ground-glass opacities were associated with adverse outcomes, whereas specific immune-mediated inflammatory disease diagnoses or immunosuppressive treatments were not.


Subject(s)
Biological Products , COVID-19 , Colitis, Ulcerative , Inflammatory Bowel Diseases , Spondylarthropathies , Biological Products/therapeutic use , COVID-19/complications , Colitis, Ulcerative/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Middle Aged , Retrospective Studies , Spondylarthropathies/drug therapy
12.
Aliment Pharmacol Ther ; 56(6): 1044-1054, 2022 09.
Article in English | MEDLINE | ID: covidwho-2032364

ABSTRACT

BACKGROUND: Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions. AIM: To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD METHODS: In this prospective cohort study, patients with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24. RESULTS: We included 82 patients with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) patients with CD and five (9.4%) with UC discontinued SC vedolizumab after a median of 18 (IQR 8-22) and 6 weeks (IQR 5-10), respectively. Four patients with CD switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median serum vedolizumab concentrations increased from 19 µg/ml at the time of the switch to 31 µg/ml 12 weeks after the switch (p < 0.005). CONCLUSIONS: Switching from IV to SC vedolizumab maintenance treatment is effective in patients with CD or UC. However, 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Antibodies, Monoclonal, Humanized , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Crohn Disease/chemically induced , Crohn Disease/drug therapy , Gastrointestinal Agents/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Phobic Disorders , Prospective Studies , Remission Induction , Treatment Outcome
13.
Can J Gastroenterol Hepatol ; 2022: 3469789, 2022.
Article in English | MEDLINE | ID: covidwho-2020493

ABSTRACT

Background: COVID-19 represents one of the most significant medical problems of our time. Aims: This study is focused on the question whether patients with inflammatory bowel disease (IBD) who receive immunotherapies are more vulnerable to respiratory tract infections and SARS-CoV-2 infections in comparison to medical staff, as a cohort with an increased infection risk, and to the general population in a COVID-19 hotspot. Methods: We analysed data regarding respiratory tract infections that were collected in our IBD registry and compared them with corresponding data from medical employees in our associated Isarklinikum hospital and from the healthy general population in Munich, Germany, over the same time frame in April and June 2020. Patients were tested for SARS-CoV-2 immunoglobulins (Ig). Results: Symptoms of respiratory tract infections occurred equally frequent in IBD patients with immunotherapies as compared to those without. Older age (>49 years), TNF-inhibitor, and ustekinumab treatment showed a significantly protective role in preventing respiratory tract symptomatic COVID-19 infections that occurred in 0.45% of all our 1.091 IBD patients. Of those, 1.8% were positive for SARS-CoV-2 Ig, identically to the general population of Munich with also 1.8% positivity. Whilst more than 3% of all COVID-19 subjects of the general population died during the first wave, none of our IBD patients died or needed referral to the ICU or oxygen treatment. Conclusions: In our study, IBD patients are as susceptible to respiratory tract infections or SARS-CoV-2 as the normal population. There is no evidence of an association between IBD therapies and increased risk of COVID-19. Interestingly, a reduced rate of COVID-19 deaths in IBD patients, the majority on immunomodulator therapy, was observed, compared to the general population. Therefore, no evidence was found to suggest that IBD medication should be withheld, and adherence should be encouraged to prevent flares. In addition to older age (>49 years), TNF inhibitors and ustekinumab show a protective role in preventing respiratory tract infections. In addition, these results add to the growing evidence that supports further investigation of TNF inhibitors as a possible treatment in the early course of severe COVID-19.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , COVID-19/epidemiology , Humans , Immunotherapy , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/therapy , SARS-CoV-2 , Seasons , Tumor Necrosis Factor Inhibitors , Ustekinumab/therapeutic use
14.
PLoS One ; 17(9): e0273612, 2022.
Article in English | MEDLINE | ID: covidwho-2009702

ABSTRACT

BACKGROUND AND AIMS: SARS-CoV-2 is a worldwide serious health problem and vaccination seems to have a crucial role in managing the COVID-19 pandemic. The aim of this prospective observational study was to monitor the trend of antibodies against SARS-CoV-2 after vaccination with BNT162b2 (COMIRNATY) in patients with inflammatory bowel disease treated by immunosuppressive and/or biological therapy, demonstrate whether any type of this therapy is associated with poorer production of antibodies against COVID-19 and evaluate the safety of vaccination against COVID-19 in these patients. METHODS: Eighty-seven eligible patients from one tertiary gastroenterological center with inflammatory bowel disease (60 with CD, 27 with UC) treated by immunosuppressive and/or biological therapy from the antiTNFα group were indicated to vaccination against SARS-CoV-2. Effectiveness of vaccination was evaluated by the values of antibodies before and 4 weeks after 2nd dose of vaccine. Additional goal was to evaluate adverse events of vaccination. RESULTS: Before the 2nd dose of vaccine, geometric mean of SARS-CoV-2 IgG antibodies were 40.7 U/ml in the biological therapy group, 34.8 U/ml in the azathioprine group and 44.8 U/ml in the combination therapy group of patients. The geometric means were 676.5.7 U/ml in the biological therapy group, 614.4 U/ml in the azathioprine group and 500.1 U/ml in the combination therapy group of patients four weeks after 2nd dose. Statistically significant differences between these groups were not proved. Several non-severe local and general adverse events were present in our patients with a majority of these events on the day of vaccine administration and the day after, no anaphylactic reactions were present. CONCLUSIONS: Our measurements proved the efficacy and safety of vaccination against SARS-CoV-2 in patients with inflammatory bowel disease treated by immunosuppressive and/or biological therapy. Statistically significant differences between our groups of patients were not proved.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Viral Vaccines , Antibodies, Viral , Azathioprine , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/drug therapy , Pandemics , SARS-CoV-2 , Vaccination
15.
Expert Rev Clin Pharmacol ; 15(10): 1243-1252, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2008460

ABSTRACT

OBJECTIVES: Patients with inflammatory bowel disease were excluded from trials that led to the approval of anti-COVID-19 vaccines and are worthy of real-life studies providing information on the safety of these vaccines in this clinical setting. METHODS: A prospective observational study was performed to estimate BNT162b2 mRNA COVID-19 Vaccine local and systemic adverse events (AEs) incidence related to administration in patients with inflammatory bowel disease through a questionnaire administered at the first, second, and third doses. Disease activity by Mayo Partial Score and Harvey-Bradshaw Index was also evaluated. RESULTS: Eighty patients with a median age of 47.5 years were initially enrolled. The local AEs rate was 26.25%, 58.75%, and 28.37% at the first, second, and third doses of the vaccine, respectively. In contrast, the systemic AEs rate was 52.2%, 48.75%, and 43.24%. Clinic-demographic predictor variables for AEs were not identified. Vaccination did not affect disease activity and no statistically significant difference in disease activity index scores was observed between the three doses. No serious adverse events were observed. CONCLUSION: This vaccine was safe in a population of patients with inflammatory bowel disease and, therefore, could be safely administered in this clinical setting.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Humans , Middle Aged , BNT162 Vaccine , RNA, Messenger , COVID-19/prevention & control , Inflammatory Bowel Diseases/drug therapy , Biological Therapy
16.
Lancet Gastroenterol Hepatol ; 7(11): 1005-1015, 2022 11.
Article in English | MEDLINE | ID: covidwho-2008221

ABSTRACT

BACKGROUND: COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose. METHODS: VIP was a multicentre, prospective, case-control study done in nine centres in the UK. We recruited immunosuppressed patients with IBD and non-immunosuppressed healthy individuals. All participants were aged 18 years or older. The healthy control group had no diagnosis of IBD and no current treatment with systemic immunosuppressive therapy for any other indication. The immunosuppressed patients with IBD had an established diagnosis of Crohn's disease, ulcerative colitis, or unclassified IBD using standard definitions of IBD, and were receiving established treatment with one of six immunosuppressive regimens for at least 12 weeks at the time of first dose of SARS-CoV-2 vaccination. All participants had to have received three doses of an approved COVID-19 vaccine. SARS-CoV-2 spike antibody binding and T-cell responses were measured in all participant groups. The primary outcome was anti-SARS-CoV-2 spike (S1 receptor binding domain [RBD]) antibody concentration 28-49 days after the third vaccine dose, adjusted by age, homologous versus heterologous vaccine schedule, and previous SARS-CoV-2 infection. The primary outcome was assessed in all participants with available data. FINDINGS: Between Oct 18, 2021, and March 29, 2022, 352 participants were included in the study (thiopurine n=65, infliximab n=46, thiopurine plus infliximab combination therapy n=49, ustekinumab n=44, vedolizumab n=50, tofacitinib n=26, and healthy controls n=72). Geometric mean anti-SARS-CoV-2 S1 RBD antibody concentrations increased in all groups following a third vaccine dose, but were significantly lower in patients treated with infliximab (2736·8 U/mL [geometric SD 4·3]; p<0·0001), infliximab plus thiopurine (1818·3 U/mL [6·7]; p<0·0001), and tofacitinib (8071·5 U/mL [3·1]; p=0·0018) compared with the healthy control group (16 774·2 U/mL [2·6]). There were no significant differences in anti-SARS-CoV-2 S1 RBD antibody concentrations between the healthy control group and patients treated with thiopurine (12 019·7 U/mL [2·2]; p=0·099), ustekinumab (11 089·3 U/mL [2·8]; p=0·060), or vedolizumab (13 564·9 U/mL [2·4]; p=0·27). In multivariable modelling, lower anti-SARS-CoV-2 S1 RBD antibody concentrations were independently associated with infliximab (geometric mean ratio 0·15 [95% CI 0·11-0·21]; p<0·0001), tofacitinib (0·52 [CI 0·31-0·87]; p=0·012), and thiopurine (0·69 [0·51-0·95]; p=0·021), but not with ustekinumab (0·64 [0·39-1·06]; p=0·083), or vedolizumab (0·84 [0·54-1·30]; p=0·43). Previous SARS-CoV-2 infection (1·58 [1·22-2·05]; p=0·0006) was independently associated with higher anti-SARS-CoV-2 S1 RBD antibody concentrations and older age (0·88 [0·80-0·97]; p=0·0073) was independently associated with lower anti-SARS-CoV-2 S1 RBD antibody concentrations. Antigen-specific T-cell responses were similar in all groups, except for recipients of tofacitinib without evidence of previous infection, where T-cell responses were significantly reduced relative to healthy controls (p=0·021). INTERPRETATION: A third dose of COVID-19 vaccine induced a boost in antibody binding in immunosuppressed patients with IBD, but these responses were reduced in patients taking infliximab, infliximab plus thiopurine, and tofacitinib. Tofacitinib was also associated with reduced T-cell responses. These findings support continued prioritisation of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF and JAK inhibitors. FUNDING: Pfizer.


Subject(s)
COVID-19 Vaccines , COVID-19 , Inflammatory Bowel Diseases , Janus Kinase Inhibitors , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Case-Control Studies , Humans , Immunosuppressive Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Prospective Studies , SARS-CoV-2 , T-Lymphocytes , Tumor Necrosis Factor Inhibitors , Ustekinumab
17.
Front Immunol ; 13: 920333, 2022.
Article in English | MEDLINE | ID: covidwho-1963484

ABSTRACT

Introduction: Patients with Inflammatory Bowel Disease (IBD) frequently receive immunomodulating treatment, which may render them at increased risk of an attenuated immune response upon vaccination. In this study, we assessed the effects of different types of commonly prescribed immunosuppressive medications on the serological response after vaccination against SARS-CoV-2 in patients with IBD. Methods: In this prospective observational cohort study, IgG antibody titers against SARS-CoV-2 were measured 2-10 weeks after completion of standard vaccination regimens in patients with IBD. Clinical characteristics, previous history of SARS-CoV-2 infection, type of vaccine (mRNA- or vector-based) and medication use were recorded at the time of sampling. Subsequently, a chemiluminescent microparticle immunoassay was used for the quantitative determination of IgG antibodies against the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Results: Three hundred and twelve (312) patients with IBD were included (172 Crohn's disease [CD] and 140 ulcerative colitis [UC]). Seroconversion (defined as titer of >50 AU/ml) was achieved in 98.3% of patients. Antibody concentrations were significantly lower in patients treated with TNF-α-antagonists vs. non-users of TNF-α-antagonists (geometric mean [95% confidence interval]: 2204 [1655-2935] vs. 5002 [4089-6116] AU/ml, P<0.001). In multivariable models, use of TNF-α-antagonists (P<0.001), vector vaccines (P<0.001), age (>50 years) (P<0.01) and CD (P<0.05) were independently associated with lower anti-SARS-CoV-2 antibody titers. In patients who received mRNA vaccines, users of thiopurines (either prescribed as monotherapy or in combination with biologicals) demonstrated significantly lower antibody titers compared to thiopurine non-users (P<0.05). Conclusion: Despite reassuring findings that most patients with IBD have detectable antibodies after anti-SARS-CoV-2 vaccination, TNF-α-antagonists were found to be strongly associated with an attenuated IgG antibody response after vaccination against SARS-CoV-2, independent of vaccine type, the time elapsed after vaccination and blood sampling, prior SARS-CoV-2 infection and patient age. Patients treated with thiopurines and receiving mRNA-based vaccines demonstrated lower anti-SARS-CoV-2 antibody titers compared with non-users.


Subject(s)
COVID-19 Vaccines , COVID-19 , Crohn Disease , Inflammatory Bowel Diseases , Tumor Necrosis Factor Inhibitors , Antibodies, Viral , Antibody Formation , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , Crohn Disease/drug therapy , Humans , Immunoglobulin G , Inflammatory Bowel Diseases/drug therapy , Middle Aged , Prospective Studies , SARS-CoV-2 , Tumor Necrosis Factor Inhibitors/therapeutic use
18.
Res Social Adm Pharm ; 18(12): 4138-4143, 2022 12.
Article in English | MEDLINE | ID: covidwho-1960005

ABSTRACT

BACKGROUND: In response to the COVID-19 pandemic, the CDC issued guidance advising patients and providers to adopt social distancing practices such as home-based infusions (H-BI). METHODS: We performed a mixed methods evaluation to summarize perceptions, concerns, and experiences with H-BI among all inflammatory bowel disease patients 18-90 years of age who transitioned to home-based infliximab or vedolizumab infusions between March to July 2020 at a tertiary care center. Semi-structured interviews were conducted and analyzed using an iterative, inductive thematic approach. Baseline characteristics and outcome on safety, COVID-19 transmission, delays in infusions, and H-BI persistence were collected. RESULTS: Of the 57 participants who transitioned to H-BI, 20 (33%) responded. Four major categories and six major themes related to expectations, experience, perceived safety, and logistical factors were identified. Initial perceptions were mixed, however these resolved. One patient developed COVID-19, one patient experienced an adverse event, 12 (21%) patients experienced an infusion delay, and 6 (11%) patients transitioned from H-BI. DISCUSSION: Despite mixed initial perceptions, respondents had a positive experience with most respondents planning to continue H-BI after the pandemic resolves. Several real-world actionable barriers were identified related to scheduling, communication between stakeholders, and nursing quality. No major safety concerns were identified.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Humans , COVID-19/epidemiology , Pandemics , Inflammatory Bowel Diseases/drug therapy , Infliximab , Chronic Disease
19.
Rheumatol Int ; 42(9): 1493-1511, 2022 09.
Article in English | MEDLINE | ID: covidwho-1941559

ABSTRACT

Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α therapy, whereas new indications have been added. Recent experimental studies have shown that anti-TNFs exert their beneficial effects not only by restoring aberrant TNF-mediated immune mechanisms, but also by de-activating pathogenic fibroblast-like mesenchymal cells. Real-world data on millions of patients further confirmed the remarkable efficacy of anti-TNFs. It is now clear that anti-TNFs alter the physical course of inflammatory arthritis and inflammatory bowel disease, leading to inhibition of local and systemic bone loss and to a decline in the number of surgeries for disease-related complications, while anti-TNFs improve morbidity and mortality, acting beneficially also on cardiovascular comorbidities. On the other hand, no new safety signals emerged, whereas anti-TNF-α safety in pregnancy and amid the COVID-19 pandemic was confirmed. The use of biosimilars was associated with cost reductions making anti-TNFs more widely available. Moreover, the current implementation of the "treat-to-target" approach and treatment de-escalation strategies of IMIDs were based on anti-TNFs. An intensive search to discover biomarkers to optimize response to anti-TNF-α treatment is currently ongoing. Finally, selective targeting of TNF-α receptors, new forms of anti-TNFs and combinations with other agents, are being tested in clinical trials and will probably expand the spectrum of TNF-α inhibition as a therapeutic strategy for IMIDs.


Subject(s)
Biosimilar Pharmaceuticals , COVID-19 , Inflammatory Bowel Diseases , Biosimilar Pharmaceuticals/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Pandemics , Tumor Necrosis Factor Inhibitors/therapeutic use , Tumor Necrosis Factor-alpha
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