Predictors of an Immunogenic Response to the BNT162b2 mRNA COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases Treated with Rituximab: A Multicenter Study

2021 ◽  
Author(s):  
Victoria Furer ◽  
Tali Eviatar ◽  
Devy Zisman ◽  
Hagit Peleg ◽  
Yolanda Braun-Moscovici ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Optimal Timing ◽  
Inflammatory Rheumatic Diseases ◽  
Inflammatory Myositis ◽  
Predicting Factors ◽  
Igg Level ◽  
Immunogenic Response ◽  
Independent Cohort

Abstract BackgroundTreatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX).MethodsWe analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls immunized with BNT162b2 mRNA vaccine participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG measured at 2 to 6 weeks after the second vaccine dose. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX patients (n=48) immunized with the BNT162b2 mRNA vaccine.Results AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from non-responders by lower number of RTX courses (median (range) 3 (1-10) vs 5 (1-15), p=0.007; lower cumulative RTX dose 6943.11±5975.74 vs 9780.95±7240.12 mg, p=0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78±576.28 vs. 884.33±302.31 mg/dL, p=0.002, and extended interval between RTX treatment and vaccination, 469.82±570.39 vs 162.08±160.12 days, p=0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046-0.96, p=0.044 and OR 0.189, 95% CI 0.036-0.987, p=0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, 63.3% positive and 88.9% negative predictive values.ConclusionsThe predicting calculator might guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients.

scholarly journals LB0003 IMMUNOGENICITY AND SAFETY OF THE BNT162b2 mRNA COVID-19 VACCINE IN ADULT PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES AND GENERAL POPULATION: A MULTICENTER STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 200-201
Author(s):  
V. Furer ◽  
T. Eviatar ◽  
D. Zisman ◽  
H. Peleg ◽  
D. Paran ◽  
...  
Keyword(s):  
General Population ◽  
Rheumatic Diseases ◽  
Vaccine Dose ◽  
Inflammatory Rheumatic Diseases ◽  
Efficacy And Safety ◽  
Post Vaccination ◽  
Seropositivity Rate ◽  
Seropositive Rate ◽  
Anti Cd20 ◽  
Immunogenic Response

Background:Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity, efficacy, and safety of the novel BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.Objectives:To investigate the immunogenicity, efficacy, and safety of the BNT162b2 mRNA vaccine in patients with AIIRD compared to the general population.Methods:A prospective multicenter study investigated immunogenicity, efficacy, and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD including rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthropathy (axSpA), systemic lupus erythematosus (SLE), connective tissues diseases (CTD), systemic vasculitides, and idiopathic inflammatory myositis (IIM), compared to control subjects without rheumatic diseases or immunosuppressive therapies. Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2 - 6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/ml. Post-vaccination efficacy defined as post-vaccination COVID-19 infection and safety were assessed. Pre- and post- vaccination disease activity indices were assessed as appropriate for each disease.Results:A total of 686 AIIRD patients and 121 controls participated into the study. AIIRD patients were significantly older than controls, mean age±SD 56.76±14.88 vs 50.76±14.68, respectively, p<0.0001. A total of 95.2% (n=653) AIIRD patients were treated with immunomodulatory medications.The seropositivity rate was 86% (n=590) in patients with AIIRD compared to 100% in controls (p <0.0001) The level of the S1/S2 antibodies was significantly reduced in AIIRD patients compared to controls (mean± SD 132.9±91.7 vs 218.6±82.06, P<0.0001). In patients with PsA, AxSpA, SLE, and LVV, the seropositive rate was above 90%. In RA, the seropositive rate was 82.1% and the lowest seropositive rate (<40%) was observed in patients with AAV and IIM.Anti-CD20 significantly impaired the vaccine’s immunogenicity, with the lowest seropositivity rate of 39%. The use of GC, mycophenolate mofetil (MMF), and abatacept was associated with a significantly lower rate of seropositivity (Figure 1). MTX significantly reduced the seropositivity in patients treated with MTX monotherapy and in combinations with other treatments (92% and 84%, respectively), although at a lesser magnitude than anti-CD20, MMF, and abatacept. More than 97% of patients treated with anti-cytokine therapies including TNFi, interleukin-17 and interleukin-6 inhibitors had an appropriate immunogenic response when used as monotherapy. The combination of TNFi with MTX significantly reduced the rate of seropositivity to 93%, p=0.04. Age over 65 years, a diagnosis of RA, IIM, ANCA-associated vascilitis, and treatment with GC, MMF, anti-CD20, and abatacept were associated with a reduced likelihood of seropositivity.Figure 1.Seropositivity rate by immunosuppressive treatment.There were no post-vaccination symptomatic cases of COVID-19 among AIIRD patients and one mild case in the control group. Major adverse events in AIIRD patients included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Post-vaccination disease activity remained stable in the majority of patients.Conclusion:Vaccination with the BNTb262 vaccine resulted in an adequate immunogenic response with an acceptable safety profile in the majority of patients with AIIRD. Treatment with GC, rituximab, MMF, and abatacept may impair BNT162b2-induced immunogenicity. Postponing administration of rituximab, when clinically feasible, seems to be reasonable to improve vaccine-induced immunogenicity. Holding treatment with abatacept and MMF may be considered on an individual basis.Disclosure of Interests:None declared

scholarly journals Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study

2021 ◽  
pp. annrheumdis-2021-220647
Author(s):  
Victoria Furer ◽  
Tali Eviatar ◽  
Devy Zisman ◽  
Hagit Peleg ◽  
Daphna Paran ◽  
...  
Keyword(s):  
General Population ◽  
Disease Activity ◽  
Rheumatic Diseases ◽  
Messenger Rna ◽  
Vaccine Dose ◽  
Adult Patients ◽  
Control Group ◽  
Inflammatory Rheumatic Diseases ◽  
Igg Antibody ◽  
Antibody Levels

IntroductionVaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.MethodsA multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2–6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose.ResultsFollowing vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients.ConclusionmRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.

scholarly journals Disease activity and humoral response in patients with inflammatory rheumatic diseases after two doses of the Pfizer mRNA vaccine against SARS-CoV-2

2021 ◽  
pp. annrheumdis-2021-220503
Author(s):  
Yolanda Braun-Moscovici ◽  
Marielle Kaplan ◽  
Maya Braun ◽  
Doron Markovits ◽  
Samy Giryes ◽  
...  
Keyword(s):  
Side Effects ◽  
Rheumatic Diseases ◽  
Messenger Rna ◽  
Disease Duration ◽  
Humoral Response ◽  
Inflammatory Rheumatic Diseases ◽  
Igg Antibodies ◽  
Activity Assessment ◽  
The Impact ◽  
Immunomodulating Drugs

BackgroundThe registration trials of messenger RNA (mRNA) vaccines against SARS-CoV-2 did not address patients with inflammatory rheumatic diseases (IRD).ObjectiveTo assess the humoral response after two doses of mRNA vaccine against SARS-CoV-2, in patients with IRD treated with immunomodulating drugs and the impact on IRD activity.MethodsConsecutive patients treated at the rheumatology institute, who received their first SARS-CoV-2 (Pfizer) vaccine, were recruited to the study, at their routine visit. They were reassessed 4–6 weeks after receiving the second dose of vaccine, and blood samples were obtained for serology. IRD activity assessment and the vaccine side effects were documented during both visits. IgG antibodies (Abs) against SARS-CoV-2 were detected using the SARS-CoV-2 IgG II Quant (Abbott) assay.ResultsTwo hundred and sixty-four patients with stable disease, (mean(SD) age 57.6 (13.18) years, disease duration 11.06 (7.42) years), were recruited. The immunomodulatory therapy was not modified before or after the vaccination. After the second vaccination, 227 patients (86%) mounted IgG Ab against SARS-CoV-2 (mean (SD) 5830.8 (8937) AU/mL) and 37 patients (14%) did not, 22/37 were treated with B cell-depleting agents. The reported side effects of the vaccine were minor. The rheumatic disease remained stable in all patients.ConclusionsThe vast majority of patients with IRD developed a significant humoral response following the administration of the second dose of the Pfizer mRNA vaccine against SARS-CoV-2 virus. Only minor side effects were reported and no apparent impact on IRD activity was noted.

scholarly journals Flavonoids: Nutraceuticals for Rheumatic Diseases via Targeting of Inflammasome Activation

2021 ◽  
Vol 22 (2) ◽  
pp. 488
Author(s):  
Young-Su Yi
Keyword(s):  
Rheumatic Diseases ◽  
Fruits And Vegetables ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Cellular Damage ◽  
Inflammatory Rheumatic Diseases ◽  
Inflammasome Activation ◽  
Central Feature ◽  
Inflammatory Protein ◽  
Anti Inflammatory

Inflammation, an innate immune response that prevents cellular damage caused by pathogens, consists of two successive mechanisms, namely priming and triggering. While priming is an inflammation-preparation step, triggering is an inflammation-activation step, and the central feature of triggering is the activation of inflammasomes and intracellular inflammatory protein complexes. Flavonoids are natural phenolic compounds predominantly present in plants, fruits, and vegetables and are known to possess strong anti-inflammatory activities. The anti-inflammatory activity of flavonoids has long been demonstrated, with the main focus on the priming mechanisms, while increasing numbers of recent studies have redirected the research focus on the triggering step, and studies have reported that flavonoids inhibit inflammatory responses and diseases by targeting inflammasome activation. Rheumatic diseases are systemic inflammatory and autoimmune diseases that primarily affect joints and connective tissues, and they are associated with numerous deleterious effects. Here, we discuss the emerging literature on the ameliorative role of flavonoids targeting inflammasome activation in inflammatory rheumatic diseases.

scholarly journals POS1260 FACTORS ASSOCIATED WITH SEVERE SARS-COV-2 INFECTION IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES IN MADRID: RESULTS FROM REUMA-COVID SORCOM REGISTRY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 914-914
Author(s):  
A. Boteanu ◽  
A. García Fernández ◽  
N. De la Torre ◽  
M. Pavia Pascual ◽  
O. Sanchez Pernaute ◽  
...  
Keyword(s):  
High Risk ◽  
Rheumatic Diseases ◽  
Connective Tissue Diseases ◽  
Severe Infection ◽  
Pulmonary Involvement ◽  
Inflammatory Rheumatic Diseases ◽  
Factors Associated ◽  
Risk Of Death ◽  
Cardiovascular Comorbidities ◽  
Male Sex

Background:Patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 may be at risk to develop a severe course of COVID-19 due to the immune dysregulation or the influence of immunomodulating drugs on the course of the infection. For a better understanding of SARS-CoV-2 infections in patients with IRD and due to the high incidence of COVID-19 in Madrid from the beginning of this pandemic infection in Spain, the Society of Rheumatology from Madrid (SORCOM) established a registry (REUMA-COVID SORCOM) shortly after the beginning of the pandemic in Spain.Objectives:To determine factors associated with severity of infection with SARS-CoV-2 in patients with inflammatory rheumatic diseases in MadridMethods:The REUMA-COVID SORCOM registry is a multicenter, retrospective, observational cohort study conducted in Madrid, a SORCOM initiative. All rheumatology departments from Madrid were invited to participate. The study includes patients with IRD presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and November 10, 2020. We consider severe infection death or need of hospitalization. Inclusion criteria was having an IRD and at least 1 of the following 4 criteria: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a SARS-CoV-2 polymerase chain reaction (PCR) test on a nasopharyngeal swab; (2) Detection of IgM or IgG anti SARS-CoV2 in a symptomatic or asymptomatic patients (3)typical thoracic computed tomography (CT) abnormalities (ground-glass opacities) in epidemic areas; (4) COVID19–typical symptoms in an epidemic zone of COVID-19.Results:As of November 10, 2020, 417 patients with IRD were included in the REUMA-COVID SORCOM registry. 5 patients were discharged for incomplete data. Of 412 patients (mean age 57 years, 87.4% Caucasian race, 66.3% female) 174 need hospitalization (42.2%) and 33 patients died (18.4% mortality in hospitalized patients). 82.3% had comorbidities. 234 (56.8%) patients were classified as inflammatory arthropathy, 133 (32.3%) had connective tissue diseases (CTD). 41.1% of the patients had a large history of IRD (> 10 years). 10.4% of patients had previously pulmonary involvement. The study includes 143 patients taking Methotrexate, 89 patients taking anti-TNFα therapy and 27 Rituximab. In the univariant analysis, no differences were seen in the severity of COVID-19 infection in patients taking methotrexate. 63% of the all patients taking Rituximab included in the registry need hospitalization and 22% of them died. Hypertension, COPD or cardiovascular disease was associated with hospitalization.Independent factors associated with COVID-19 hospitalization in the multivariate analysis was: age (>62 years), male sex, IMC >30, previous cardiovascular comorbidities and the IRD disease duration (> 10 years). Independent factors associated with COVID-19 related death was: age (> 62 years), having a CTD diagnose, pulmonary involvement before infection and chronical GC treatment.Conclusion:Patients with IRD represent a population of particular interest in the pandemic context because the baseline immunological alteration and the treated with immunosuppressants agents they receive, comorbidities and the well-known risk of severe infection. Older age, male sex, cardiovascular comorbidities were factors associated with high risk of hospitalization in IRD patients. CTD diseases, previously pulmonary involvement and chronical GC treatment with more than 10mg/day were associated with high risk of death. Neither anti TNF-α treatment nor Methotrexate were risk factor for hospitalization or death COVID-19 related in IRD patients.Disclosure of Interests:None declared

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