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Background IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARS-CoV-2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods Clinical data and sera were collected from, 2,213 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, the United Kingdom, and the United States between, 26 May, 2020 and, 24 September, 2021 (Table, 1). Sera were taken prior to vaccination. Clinical data were collected through patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed, 99.4% concordance. Univariate analysis was performed to evaluate association between individual variables and sero-status. Results The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from, 0% in Hong Kong to, 57.9% in New Delhi, India (p<0.001). Rates in Europe and North America were similar (range, 3.57%-8.94%). Overall, SARS-CoV-2 seroprevalence appears to be equal to or less than local populations (Table, 2). Seroprevalence rates were associated with IBD type (7.8% CD, 12.4% UC, 15% IBD-U, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any IMM (p<0.001). (Table, 3). Whilst there were no significant differences in seroprevalence between patients receiving infliximab (IFX), vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on IFX monotherapy and combination therapy (both p=0.002) and VDZ (p=0.02), compared with no medications (Figure 1). Conclusion We confirm in diverse poulations that exposure to biologics or immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination.
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Background: IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARSCoV- 2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods: Clinical data and sera were collected from 2,241 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, United Kingdom, and the United States between May 2020 and September 2021 (Table 1). Sera were taken prior to vaccination. Clinical data were collected from patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed 99.4% concordance. We performed univariate analysis to evaluate association between variables and sero-status. Results: The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from 0% in Hong Kong, China, to 57.9% in New Delhi, India. Rates in Europe and North America were similar (range 3.6%-8.9%). Overall, SARSCoV- 2 seroprevalence appears to be equal to or less than local populations (Table 1). Seroprevalence rates were associated with IBD type (Crohn's disease 7.8%, ulcerative colitis 12.4%, IBD-unclassified 15.0%, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any immunomodulator (IMM) (p<0.001) (Table 1). Infection as indicated by seropositivity in the absence of known COVID infection occurred in 7.3% of patients. Whilst there were no significant differences in seroprevalence between patients receiving anti-tumor necrosis factor (anti-TNF) medications, vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on anti-TNF monotherapy (p=0.002), anti-TNF + IMM combination therapy (p=0.002), and VDZ (p=0.02), compared with no medications (Figure 1). Conclusion: We confirm in diverse populations that exposure to anti-TNFs, vedolizumab and immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination. (Table Presented) Table 1. Seroprevalence of total anti-SARS-CoV-2 spike antibodies in IBD patients by ICARUS centre with non-IBD controls noted for New Delhi, India, and publicly reported local seroprevalence and by selected patient characteristics.(Figure Presented) Figure 1. Antibody levels by medication group.
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Background: Patients with inflammatory bowel disease (IBD), either Crohn's disease (CD) or ulcerative colitis (UC), treated with immunosuppressants and/or biotherapy might have an altered immune response to SARS-CoV-2 infection. The aim of this study was to evaluate the incidence of COVID-19 in a French cohort of IBD patients treated with infliximab or vedolizumab during the first epidemic wave and to identify factors associated with the risk of infection. Methods: All patients with IBD treated with infliximab or vedolizumab from March to June 2020 in 16 French centres were included and followed for 6 months. At baseline, clinical, demographic, family and socio-professional data were collected. At each of their day hospitalization, patients reported the occurrence of symptoms of COVID-19, and the performance of a diagnostic test, if so. Serum was collected at each visit to detect immunisation by SARS-CoV-2 at the end of follow-up and to measure trough levels. Peripheral blood lymphocytes (PBLs) were frozen at each visit for 50% of patients to further analyse the immunological changes associated with COVID-19. Results: 1079 patients were included (CD n=690, mean age 41.6 years, mean disease duration 13.3 years). Clinical and demographic data at baseline are detailed in Tables 1 and 2, respectively. 143 patients (13.3%) had one or more co-morbidities associated with a risk of severe COVID-19 (hypertension 5.6%, chronic lung disease 5%, diabetes 2.4%, obesity 0.3%). Over the 6 months of followup, 458 patients (42%) had active disease defined by an HBI score >4 or Mayo score >2 and/or treatment optimisation (dose increase, shortening of infusion interval, addition of an immunosuppressant or change of biotherapy). 111 patients (10.2%) received corticosteroids at least occasionally (self-medication was not excluded). 341 patients (32%) were tested for COVID-19 by nasal swab, of whom 23 were positive. Three patients were hospitalized. Regarding serology, in the first 13 centres analysed hitherto (886 patients), 20 patients were seropositive at the end of follow-up before the start of the vaccination campaign (January 2021), i.e. 2.2%, compared to 4.5% in the general population at the same period according to Santé Publique France data. Conclusion: The preliminary analysis of this French cohort confirms that patients with IBD are not at higher risk of severe COVID-19 despite the use of biotherapy and repeated hospital stays. This population was significantly less infected than the general population. Clinical, demographic and immunological factors associated with SARS-CoV-2 infection are being analysed as well as factors associated with a lower incidence of infection compared to the general population. (Table Presented) (Table Presented)
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Background: Patients with Inflammatory Bowel Disease (IBD), either Crohn's Disease (CD) or Ulcerative Colitis (UC), treated with immunosuppressants and/or biotherapy might have an altered immune response to SARS-CoV-2 infection. The aim of this study was to evaluate the incidence of COVID-19 in a French cohort of IBD patients treated with infliximab or vedolizumab during the first epidemic wave and to identify factors associated with the risk of infection. Methods: All patients with IBD treated with infliximab or vedolizumab from March to June 2020 in 16 French centres were included and followed for 6 months. At baseline, clinical, demographic, family and socio-professional data were collected. At each of their day hospitalization, patients reported the occurrence of symptoms of COVID-19, and the performance of a diagnostic test, if so. Serum was collected at each visit to detect immunisation by SARS-CoV-2 at the end of follow-up and to measure trough levels. Peripheral blood lymphocytes (PBLs) were frozen at each visit for 50% of patients to further analyse the immunological changes associated with COVID-19. Results: 1079 patients were included (CD n=690, mean age 41.6 years, mean disease duration 13.3 years). Clinical and demographic data at baseline are detailed in Tables 1 and 2, respectively. 143 patients (13.3%) had one or more co-morbidities associated with a risk of severe COVID-19 (hypertension 5.6%, chronic lung disease 5%, diabetes 2.4%, obesity 0.3%). Over the 6 months of follow-up, 458 patients (42%) had active disease defined by an HBI score >4 or Mayo score >2 and/or treatment optimisation (dose increase, shortening of infusion interval, addition of an immunosuppressant or change of biotherapy). 111 patients (10.2%) received corticosteroids at least occasionally (self-medication was not excluded). 341 patients (32%) were tested for COVID-19 by nasal swab, of whom 23 were positive. Three patients were hospitalized. Regarding serology, in the first 13 centres analysed hitherto (886 patients), 20 patients were seropositive at the end of follow-up before the start of the vaccination campaign (January 2021), i.e. 2.2%, compared to 4.5% in the general population at the same period according to Santé Publique France data. Conclusion: The preliminary analysis of this French cohort confirms that patients with IBD are not at higher risk of severe COVID-19 despite the use of biotherapy and repeated hospital stays. This population was significantly less infected than the general population. Clinical, demographic and immunological factors associated with SARS-CoV-2 infection are being analysed as well as factors associated with a lower incidence of infection compared to the general population.
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Background: In the context of the Sars-Cov2 pandemic, the management of patients with chronic diseases and/or receiving immunosuppressive drugs was of concern due to lack of data to dictate their management. The objectives of our study were to evaluate the characteristics and prognosis of COVID-19 among IBD patients and to study the factors associated with severe COVID-19. Methods: We carried out a multicentre bispective study in 30 French GETAID centres. Participating centres were asked to report all consecutive COVID19 cases occurring in their IBD-cohort between March,1st and December,31st 2020. The cases had to be confirmed by a PCR test, or by a chest CT scan demonstrating COVID19 lesions. In addition to the baseline examination, patients were scheduled for a follow up visit within 3-6 months following their infection. Demographics, disease characteristics, treatments, and the clinical course of IBD were prospectively recorded. Severe COVID-19 was defined as admission to the hospital >1 day and/or use of oxygen therapy and/or death. Predictive factors for developing severe COVID-19 were explored using univariate and multivariate logistic regression. Results: A total of 719 IBD patients with COVID 19 were included;54.2% were women, median age was 42 years, 64.4% had Crohn's disease (CD), and median disease duration was 10.8 years. 13.3% of the patients were active smokers;12.7% had a BMI>30. With respect to the treatment, 72(10%) patients were not on any IBD medication, 75(10.4%) were only receiving 5-ASA, 164(22.8%) received conventional immunosuppressants, and 509(70.8%) biologics.21.6% of the patients developed either diarrhoea in remitters, or an exacerbation of diarrhoea in active patients. IBD treatments were maintained unchanged, suspended or discontinued in 73.4%, 25.5%, and 1.1% of the patients. Over the follow-up period, 13.2% of the patients had a flare. A total of 68 patients developed severe COVID 19, 67(9.3%) were hospitalized for a median duration of 6 days, and 4(0.6%) patients died. In multivariate analysis, age > 50 years (OR: 2.0,CI:1.06-3.72;p=0.031), obesity (OR: 2.01,CI:1.05-4.09;p=0.037), and comorbidities (OR: 3.28,CI:1.76-6.09;p=0.0002) were factors associated with the occurrence of severe COVID 19;while immunomodulatory treatment (biologic and/or immunosuppressant) was a protective factor for developing severe COVID 19 (OR: 0.38,CI: 0.22-0.69;p=0.0012). Conclusion: Rate of severe COVID 19 in this cohort of IBD patients was corresponding to the general population with similar risk factors for severity, i.e., age, obesity and comorbidities. Prescription of immunomodulators was protective against severe COVID 19, raising the hypothesis of their potential immunological effect on the immune storm phase of Sars-Cov2.
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Introduction: Subcutaneous biotherapies (SCB) are used in the management of inflammatory bowel diseases (IBD). Aims & Methods: The aims were to evaluate the feasibility in using a medication dispense data to identify these patients and to study the impact of COVID-19 on SCB prescription. LRx contains all anonymized medication dispenses prescribed in outpatient care in a representative panel of French retails pharmacies, including data of near 40 million patients. Each patient having at least a dispense of SCB or synthetic targeted treatment reimbursed in psoriasis, IBD, and chronic inflammatory rheumatologic disease was selected in 2019. An algorithm was constructed using different steps in order to classify the patient in one of these diseases (weighted score according to the step: mono-indication or common indication shared among product, prescriber's specialist, specific tracking drugs to one of these disease prescribed prior or co-prescribed with the treatment of interest). We numbered 190,640 patients of which 16% with IBD under SCB. We described IBD population in terms of demographics, SCB and co-treatment prescribed in 2019 (at least one delivery) in 2019. The impact of COVID-19 on SCB initiation was studied during the lockdown period in France (W12-W19 2020). Results: 30,788 IBD patients were under SCB in France in 2019 (52% female;5.7%, 44.1%, 34.6%, 12.0%, 2.5% of patients split in the following age classes: 0-19, 20-39, 40-59, 60-74, ≥75 years, respectively). Patients were mainly under adalimumab (82.8%), followed by ustekinumab (11.8%), and golimumab (7.3%). Azathioprine represented the most frequent immunosuppressant delivered (19.9%) followed by methotrexate (5%). Oral and rectal corticosteroids was prescribed at least once in 2019 for 45.5 and 10.4% of the patients, respectively. Oral corticosteroids delivered at least thrice concerned 6.7% of the patients. Mesalazine and sulfasalazine were delivered for 21.5% and 0.7% of the patients, respectively. The impact of SCB initiation during the lockdown period due to COVID-19 had significantly decrease by 20% compared to 2019 (p=0.003). Conclusion: The algorithm was able to identify IBD patients under SCB and could provide meaningful information in order to describe the drug survival, the change in management at the national level (for patients followed in outpatient care, only), and the impact of COVID-19. These results need to be confirmed using another source of data containing clinical diagnosis to validate the algorithm in its ability to identify chronic inflammatory diseases.
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Background: Discriminating chronic inflammatory diseases under biotherapy and/or targeted synthetic treatments (B/TST) using medico-administrative databases are challenging but required for medico-economic analyses focusing on these diseases. Objectives: The objective was to evaluate the feasibility of using a medication dispense data in order to identify patients with chronic inflammatory diseases under B/TST in outpatient care setting and evaluate the impact of COVID-19 in France Methods: LRx contains all anonymized medication dispenses prescribed in outpatient care in a representative panel of French retails pharmacies, including data of near 40 million patients. Patients having at least one B/TST delivered in 2019 were selected. An algorithm was constructed using different steps, including a machine learning step by transfer learning applied in patient classified as having a rheumatologic condition in order to differentiate rheumatoid arthritis (RA) from spondyloarthritis (SA). We numbered 190,640 patients, of which 87.8% were classified in one of the following diseases: RA, SA, psoriatic arthritis (PA), psoriasis, inflammatory bowel diseases (IBD) (extrapolated data to France). Descriptive analysis was performed. The impact of COVID-19 on biotherapy initiation was evaluated during the lockdown period (W2-W19 2020) in these different conditions. Results: Among the 167,468 patients under B/TST, 20.7%, 18.4%, 6.5%, 37.9% and 16.5% were considered as having a psoriasis, IBD, PA, RA, and SA, respectively. Female patients were more frequent in RA and PA (≥ 60%);younger (< 20 years) and older patients (74 years) were found in patients with IBD (5.7%) and RA (12.6%), respectively. Contrasting with IBD, SA, and RA patients were mainly under anti-TNF treatment (≥ 90% for IBD and SA, 73.5% for RA), psoriasis and PA patients received a range of broadly well-balanced of B/TST. Among the immunosuppressant, methotrexate was mostly prescribed in RA (58.4%), PA (34.1%), and psoriasis (14.1%), and azathioprine in IBD (19.9%). Oral corticosteroid delivered at least 4 times in 2019 were mostly found to be associated with a RA condition (28%). A significant decrease of biotherapy initiation was observed during the lockdown in France in patients with IBD (-20%, p=0.03) and psoriasis (-54%, p<0.0001), not significant decrease in patients with SA (-6%) and increase in RA patients (+23%). Conclusion: The algorithm was able to identify patients with chronic inflammatory diseases under B/TST delivered in outpatient care and will allow to follow-up its management and study the COVID-19 impact on biotherapy initiation. An external validation needs to be performed .
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Background: During the epidemic's peak of COVID-19, scientific societies published recommendations on biotherapy and targeted synthetic treatment (B/TST) use in patients with chronic articular inflammatory diseases, inflammatory bowel diseases, and psoriasis. Objectives: The objective was to evaluate the impact of COVID-19 in France on initiation and renewal of B/TST. Methods: LRx contains all anonymized medication dispenses prescribed in outpatient care in a representative panel of French retails pharmacies, including data of near 40 million patients. The impact of B/TST initiation and renewal were studied using 2019 as reference and dispense deliveries data of pharmacies with regular flew in order to perform the comparison. B/TST considered were abatacept, anti-TNF, anti-IL6, anti-IL17, anti-IL12/23 or anti-IL23, JAK inhibitors (JAKi) and other classes such as aprelimast, aminosalicylates (AS), hydroxychloroquine (HCQ), and methotrexate (MTX). A treatment initiated was defined as a treatment not delivered in the past 12 months, and conversely for a treatment renewal. Results were presented as raw one and expressed in percentage of patients having at least one B/TST delivery in each therapeutic classes of interest in 2020 compared to 2019 used as reference year (period from week 12 to week 19 considered and corresponding to the lockdown period in France). Results: During the lockdown period, a decrease in initiation was observed for patients treated with: abatacept (405 in 2019 vs 227 in 2020: -44%, p<0.001), anti-TNF (1156 vs 1058, -31%, p<0.001), anti-IL17 (415 vs 206, -50%, p<0.001), anti-IL12-23 (395 vs 339, -12%, p=0.16), JAKi (289 vs 174, -39%, p=0.006), contrasting with an increase for Tociliumab (117 vs 445, +152%, p=0,01). We found a decrease of 7% (2171 vs 2015, p=0,35), 44% (405 vs 227, p<0.001), 30% (3430 vs 2390, p p<0.001) of AS, aprelimast and MTX initiation, respectively, and an increase of 173% (1708 vs 4671, p=0.11) of HCQ initiation. No decrease for the renewal of B/TST was observed Conclusion: During the epidemic's peak, initiation of AS, MTX, biotherapies (except for tocilizumab), and JAKi dramatically decreased without impacting their renewal. Two treatments were mainly initiated, tocilizumab probably due to a switch from intravenous to subcutaneous injection and HCQ in relation to its presumably effect on COVID-19. Overall, recommendations from scientific societies have been followed.
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Introduction Plusieurs sociétés savantes, dont la SFR et l’EULAR, ont émis des recommandations sur le renouvellement et l’initiation des biothérapies (B) et des traitements synthétiques ciblés (TSC) pour les patients souffrant d’une maladie inflammatoire chronique (MIC) au pic de l’épidémie. Nous avons étudié le profil de délivrances de ces traitements durant la période de confinement en France. Matériels et méthodes Nous avons utilisé la source de données d’IQVIA, LTD, Longitudinal Treatment Dynamics, qui comprend les données de délivrances d’un échantillon représentatif de 45 % des officines françaises. Toutes les B/TSC prescrites par les spécialités habilitées à le faire et délivrées en ville ont été prises en considération. L’impact national des renouvellements et des initiations de ces traitements a été étudié pendant la période de confinement (Semaine S12 à S19) et comparé à la même période en 2019 à partir des données de délivrance des pharmacies ayant transmis leur donnée régulièrement pendant la période d’intérêt (36 % des pharmacies françaises). Les résultats sont présentés à partir des données brutes et exprimés en pourcentage de patients ayant eu une délivrance des classes thérapeutiques d’intérêt en 2020 comparé à 2019 utilisée comme année de référence (Fig. 1). Les classes prises en considération ont été les biothérapies (anti-TNF, anti-IL6, anti-IL17, anti-IL23), les traitements synthétiques ciblés (aprélimast, inhibiteurs de JAK), ainsi que des traitements susceptibles d’être utilisés dans les MIC, à savoir les aminosalicylés, l’hydroxychloroquine et le méthotrexate. Résultats Pendant la période S12 à S19, 48341 et 53944 patients ont eu au moins une délivrance d’un B/TSC respectivement en 2019 et 2020. La période de confinement n’a pas eu d’impact sur les renouvellements de B/TSC comparés à 2019 quelque soit le type de prescripteur ou la molécule prescrite. En revanche pour les initiations, elles ont diminué pour la majorité des classes suivantes dont les anti-TNF (−31 %), les anti-IL17 (− 50 %), les anti-IL23 (−12 %) et les TSC (−42 %) sauf pour les ant-IL6 (+152 %, augmentation concernant exclusivement le tocilizumab). Concernant les autres traitements, les initiations ont diminué pour les aminosalicylés (−7 %) et le méthotrexate (−30 %) et fortement augmenté pour l’hydroxychloroquine (+173 %). Conclusion Au pic de l’épidémie, les initiations par aminosalicylés, méthotrexate, biothérapie (sauf tocilizumab) et TSC ont fortement diminué sans impact sur les renouvellements de ces traitements. Deux molécules ont été fortement prescrites en initiation, le tocilizumab probablement lié au switch vers la voie sous cutanée et l’hydroxychloroquine dans l’hypothèse d’un effet sur la COVID-19. Les recommmandations préconisées par les différentes sociétés savantes semblent avoir été respectées pour ce qui concerne les B/TSC. Des analyses par MIC devraient être réalisées pour compléter ces données.