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.

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 Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001041 ◽  
Author(s):  
Victoria Furer ◽  
Christien Rondaan ◽  
Marloes Heijstek ◽  
Sander van Assen ◽  
Marc Bijl ◽  
...  
Keyword(s):  
General Population ◽  
Hepatitis B ◽  
Incidence Rate ◽  
Rheumatic Diseases ◽  
Pneumococcal Disease ◽  
Hpv Infection ◽  
Adult Patients ◽  
Current Evidence ◽  
Inflammatory Rheumatic Diseases ◽  
Pooled Prevalence

ObjectivesThe aims of this study were to update the evidence on the incidence and prevalence rates of vaccine preventable infections (VPI) in patients with autoimmune inflammatory rheumatic diseases (AIIRD) and compare the data to the general population when available.MethodsA literature search was performed using Medline, Embase and Cochrane library (October 2009 to August 2018). The primary outcome was the incidence or prevalence of VPI in the adult AIIRD population. Meta-analysis was performed when appropriate.ResultsSixty-three publications out of 3876 identified records met the inclusion criteria: influenza (n=4), pneumococcal disease (n=7), hepatitis B (n=10), herpes zoster (HZ) (n=29), human papillomavirus (HPV) infection (n=13). An increased incidence of influenza and pneumococcal disease was reported in patients with AIIRD. HZ infection-pooled incidence rate ratio (IRR) was 2.9 (95% CI 2.4 to 3.3) in patients with AIIRD versus general population. Among AIIRD, inflammatory myositis conferred the highest incidence rate (IR) of HZ (pooled IRR 5.1, 95% CI 4.3 to 5.9), followed by systemic lupus erythematosus (SLE) (pooled IRR 4.0, 95% CI 2.3 to 5.7) and rheumatoid arthritis (pooled IRR 2.3, 95% CI 2.1 to 2.6). HPV infection-pooled prevalence ratio was 1.6, 95% CI 0.7 to 3.4 versus general population, based on studies mainly conducted in the SLE population in Latin America and Asia. Pooled prevalence of hepatitis B surface antigen and hepatitis B core antibody in patients with AIIRD was similar to the general population, 3%, 95% CI 1% to 5% and 15%, 95% CI 7% to 26%, respectively.ConclusionCurrent evidence shows an increased risk of VPI in patients with AIIRD, emphasising that prevention of infections is essential in these patients.

scholarly journals Mortality in Inflammatory Rheumatic Diseases: Lithuanian National Registry Data and Systematic Review

2021 ◽  
Vol 18 (23) ◽  
pp. 12338
Author(s):  
Jolanta Dadonienė ◽  
Greta Charukevič ◽  
Gabija Jasionytė ◽  
Karolina Staškuvienė ◽  
Dalia Miltinienė
Keyword(s):  
General Population ◽  
Life Expectancy ◽  
Literature Review ◽  
Rheumatic Diseases ◽  
Systematic Literature Review ◽  
Causes Of Death ◽  
Connective Tissue Diseases ◽  
Standardized Mortality Ratio ◽  
Inflammatory Rheumatic Diseases ◽  
Total Cohort

Despite significant improvement in survival, rheumatic diseases (RD) are associated with premature mortality rates comparable to cardiovascular and neoplastic disorders. The aim of our study was to assess mortality, causes of death, and life expectancy in an inflammatory RD retrospective cohort and compare those with the general population as well as with the results of previously published studies in a systematic literature review. Patients with the first-time diagnosis of inflammatory RD during 2012–2019 were identified and cross-checked for their vital status and the date of death. Sex- and age-standardized mortality ratios (SMR) as well as life expectancy for patients with inflammatory RDs were calculated. The results of a systematic literature review were included in meta-standardized mortality ratio calculations. 11,636 patients with newly diagnosed RD were identified. During a total of 43,064.34 person-years of follow-up, 950 death cases occurred. The prevailing causes of death for the total cohort were cardiovascular diseases and neoplasms. The age- and sex-adjusted SMR for the total cohort was calculated to be 1.32 (1.23; 1.40). Patients with rheumatoid arthritis if diagnosed at age 18–19 tend to live for 1.63 years less than the general population, patients with spondyloarthritis—for 2.7 years less, patients with connective tissue diseases—for almost nine years less than the general population. The findings of our study support the hypothesis that patients with RD have a higher risk of mortality and lower life expectancy than the general population.

scholarly journals Point of view on the vaccination against COVID-19 in patients with autoimmune inflammatory rheumatic diseases

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001594
Author(s):  
Victoria Furer ◽  
Christien Rondaan ◽  
Nancy Agmon-Levin ◽  
Sander van Assen ◽  
Marc Bijl ◽  
...  
Keyword(s):  
Expert Opinion ◽  
Rheumatic Diseases ◽  
Current Data ◽  
Position Paper ◽  
Point Of View ◽  
Inflammatory Rheumatic Diseases ◽  
Efficacy And Safety

In view of the COVID-19 pandemic, there is an unmet clinical need for the guidelines on vaccination of patients with autoimmune inflammatory rheumatic diseases (AIIRD). This position paper summarises the current data on COVID-19 infection in patients with AIIRD and development of vaccines against COVID-19, discusses the aspects of efficacy and safety of vaccination, and proposes preliminary considerations on vaccination against COVID-19 in patients with AIIRD, mainly based on the expert opinion and knowledge on the use of other vaccines in this population of patients.

scholarly journals Biologic agents for rheumatic diseases in the break of COVID-19: friend or foe?

2020 ◽  
Author(s):  
Cristiana Sieiro Santos ◽  
Xenia Casas Fernandez ◽  
Clara Moriano Morales ◽  
Elvira Alvarez Diez ◽  
Carolina Alvarez Castro ◽  
...  
Keyword(s):  
General Population ◽  
Hospital Admission ◽  
Infection Rate ◽  
Rheumatic Diseases ◽  
Hospital Care ◽  
Biological Therapy ◽  
Biologic Agents ◽  
Inflammatory Rheumatic Diseases ◽  
Great Opportunity ◽  
Rheumatic Patients

Background: The recent outbreak of COVID19 has raised concerns in the rheumatology community about the management of immunosuppressive patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biologic agents may suppose a risk or protection against SARSCoV2 infection however, it has been suggested that severe respiratory forms of COVID19 occur as result of exacerbated inflammation status and cytokine production. This prompted the use of IL6 (tocilizumab and sarilumab) and IL1 inhibitors (anakinra) in severe COVID19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARSCoV2. Objectives: To estimate COVID19 infection rate in patients treated with biologic agents for rheumatic inflammatory diseases, determine the influence of biologic agents treatment as a risk or protective factor and studying the prognosis of rheumatic patients receiving biologic agents compared to general population in a third level Hospital setting in Leon, Spain. Methods: We performed a retrospective observational study including patients seen at Rheumatology department who received biological therapy for rheumatic diseases between December 1st 2019 and June 1st 2020 and analysed COVID19 infection rate. All patients being attended at the rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biologic agents were included. Main variable was the hospital admission related to COVID19. The covariates were age, sex, comorbidities, biologic agent and need for hospitalization. We performed a multivariate logistic regression model to assess risk factors of hospital admission. Results: There was a total of 3711 patients with COVID19 requiring hospitalization. 30 patients out of a total of 820 patients (3.6%) receiving biological therapy had contracted COVID19 and four required hospital care. Crude incidence rate of COVID19 requiring hospital care among the general population was 2.75%, and it was 0.48% among the group with underlying rheumatic diseases. A total of 423 patients died, 2 of which received treatment with biologic agents. Patients who tested positive for COVID19 were older (female: median age 61.8 IQR 46.5 to 75; male: median age 68 IQR 48.5 to 72) than those who were negative for COVID19 (female: median age 58.4 IQR 48 to 69; male: median age 55.9 IQR 46 to 66) and more likely to have cardiovascular disease (27 % vs 10%, OR 3. 41 (CI 1.47 to 7.94), p 0.004), be active smokers (13% vs 5%, OR 3.14 (CI 1.04 to 9.47), p 0.04) and receiving treatment with IL-12/23 inhibitors (6.7% vs 1.4%, OR 5.06 (CI 1.07 to 23.91) and rituximab (13% vs 2%, 2.66 (CI 1.03 to 7.27), p 0.04) and were less likely to be receiving treatment with IL6 inhibitors (0% vs 14%, CI (0.006 to 0.97, p <0.05). When exploring the effect of the rest of the therapies between groups (affected patients vs unaffected), we found no significant differences in bsDMARD proportions. IL1 inhibitors, IL6 inhibitors, JAK inhibitors and belimumab treated patients showed the lowest incidence of COVID19 among adult rheumatic patients. We found no differences in sex or rheumatological disease between patients who tested positive for COVID19 and patients who tested negative were found. Conclusions: Our findings suggest that use of biological therapy does not associate with severe manifestations of COVID19, and it is likely to have a protective effect against them when compared to the general population.

scholarly journals Biological agents for rheumatic diseases in the outbreak of COVID-19: friend or foe?

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001439
Author(s):  
Cristiana Sieiro Santos ◽  
Xenia Cásas Férnandez ◽  
Clara Moriano Morales ◽  
Elvira Díez Álvarez ◽  
Carolina Álvarez Castro ◽  
...  
Keyword(s):  
General Population ◽  
Rheumatic Disease ◽  
Infection Rate ◽  
Rheumatic Diseases ◽  
Hospital Care ◽  
Biological Agents ◽  
Inflammatory Rheumatic Diseases ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

BackgroundThe recent outbreak of COVID-19 has raised concerns in the rheumatology community about the management of immunosuppressed patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biological agents may suppose a risk or protection against SARS-CoV-2 infection; however, it has been suggested that severe respiratory forms of COVID-19 occur as a result of exacerbated inflammation status and cytokine production. This prompted the use of interleukin 6 (IL-6) (tocilizumab and sarilumab) and IL-1 inhibitors (anakinra) in severe COVID-19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARS-CoV-2.ObjectivesTo estimate COVID-19 infection rate in patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) for inflammatory rheumatic diseases (RMD), determine the influence of biological agents treatment as risk or protective factors and study the prognosis of patients with rheumatic diseases receiving biological agents compared to the general population in a third-level hospital setting in León, Spain.MethodsWe performed a retrospective observational study including patients seen at our rheumatology department who received bDMARDs for rheumatic diseases between December 1st 2019 and December 1st 2020, and analysed COVID-19 infection rate. All patients who attended our rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biological agents were included. Main variable was the hospital admission related to COVID-19. The covariates were age, sex, comorbidities, biological agent, duration of treatment, mean dose of glucocorticoids and need for intensive care unit . We performed an univariate and multivariate logistic regression models to assess risk factors of COVID-19 infection.ResultsThere were a total of 4464 patients with COVID-19 requiring hospitalisation. 40 patients out of a total of 820 patients with rheumatic diseases (4.8%) receiving bDMARDs contracted COVID-19 and 4 required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 3.6%, and it was 0.89% among the group with underlying rheumatic diseases. 90% of patients receiving bDMARDS with COVID-19 did not require hospitalisation. Out of the 4464 patients, 869 patients died, 2 of which received treatment with biological agents. Patients with rheumatic diseases who tested positive for COVID-19 were older (female: median age 60.8 IQR 46-74; male: median age 61.9 IQR 52-70.3) than those who were negative for COVID-19 (female: median age 58.3 IQR 48-69; male: median age 56.2 IQR 47-66), more likely to have hypertension (45% vs 26%, OR 2.25 (CI 1.18-4.27),p 0.02), cardiovascular disease (23 % vs 9.6%, OR 2.73 (1.25-5.95), p 0.02), be smokers (13% vs 4.6%, OR 2.95 (CI 1.09-7.98), p 0.04), receiving treatment with rituximab (20% vs 8%, 2.28 (CI 1.24-6.32), p 0.02) and a higher dose of glucocorticoids (OR 2.5 (1.3-10.33, p 0.02) and were less likely to be receiving treatment with IL-6 inhibitors (2.5% vs 14%, OR 0.16, (CI 0.10-0.97, p 0.03). When exploring the effect of the rest of the therapies between groups (affected patients vs unaffected), we found no significant differences in bDMARD proportions. IL-1 inhibitors, IL-6 inhibitors, JAK inhibitors and belimumab-treated patients showed the lowest incidence of COVID-19 among adult patients with rheumatic diseases. We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative.ConclusionsOverall, the use of biological disease-modifying antirheumatic drugs (bDMARDs) does not associate with severe manifestations of COVID-19. Patients with rheumatic disease diagnosed with COVID-19 were more likely to be receiving a higher dose of glucocorticoids and treatment with rituximab. IL-6 inhibitors may have a protective effect.

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