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Background: Adolescents with juvenile-onset autoimmune infammatory rheumatic diseases (AIIRD) could be at risk for disease fare secondary to SARS-CoV-2 infection or to withholding anti-infammatory therapy. While vaccination can protect against COVID-19, safety and immunogenicity data regarding anti-SARS-CoV-2 vaccines among adolescents with AIIRD are limited. Objectives: This international, prospective, multicentre study evaluated the safety and immunogenicity of the BNT162b2 anti-SARS-CoV-2 vaccine among adolescents and young adults with juvenile-onset AIIRD, 80% of whom are on chronic immunomodulatory therapy. Methods: Vaccine side effects, disease activity, and short-term efficacy were evaluated after 3 months in 91 patients. Anti-spike S1/S2 IgG antibody levels were evaluated in 37 patients and 22 controls, 2-9 weeks after the second dose. Results: Ninety-one patients and 40 healthy controls were included. Safety pro-file was good, with 96.7% (n=88) of patients reporting mild or no side-effects, and no change in disease activity. However, 3 patients had transient acute symptoms: 2 following the frst vaccination (renal failure and pulmonary haemorrhage) and 1 following the second dose (mild lupus fare vs. viral infection). Seropositivity rate was 97.3% in the AIIRD group compared with 100% among controls. However, anti-S1/S2 antibody titres were signifcantly lower in the AIIRD group compared with controls (242±136.4 vs. 387.8±57.3 BAU/ml, respectively;p<0.0001). No cases of COVID-19 were documented during the 3-month follow-up. Conclusion: Vaccination of juvenile-onset AIIRD patients demonstrated good short-term safety and efficacy, high seropositivity rate, but lower anti-S1/S2 antibody titres compared to healthy controls. These results should encourage vaccination of adolescents with juvenile-onset AIIRD, even while on immunomodulation.
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Background: Data on the effect of secukinumab on the humoral response to the BNT162b2 mRNA vaccine are limited. Objectives: We aimed to assess prospectively the humoral response to the BNT162b2 mRNA vaccine in patients with spondyloarthritis (SpA) treated with secukinumab in comparison to immunocompetent controls. Methods: Patients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with secukinumab for at least 3 months and immunocompetent controls were vaccinated with two-dose regimen of the BNT162b2 mRNA vaccine. Clinical and laboratory assessments were performed at 2-8 weeks [SpA: 37 on secukinumab, (median age 53% female), 122 controls (median age 53, 51% female)], and 6 months [SpA: 27 on secukinumab, 116 controls] after the second vaccine dose. A subgroup of patients (22 SpA on secukinumab, 45 controls) were evaluated after the third vaccine dose. The seropositive response was defned as a detectable S1/S2 IgG ≥15 binding antibody units (BAU)/ml. Results: The two-dose vaccine regimen induced a similar immunogenic response in patients and controls refected by the seropositivity rates of 100% in both groups. After six months, the rate of seropositivity remained as high as 96% in both secukinumab-treated patients and immunocompetent controls. The decline of S1/S2 IgG titer within six months was similar in controls and secukinumab-treated patients,-66.4 (95% CI {-70.9,-39.9}) and-55 BAU/ml (95% CI {-95.42,-36.87)). Following the third vaccine, the seropositivity rate increased to 100 % in both groups. At all-time points, S1/S2 IgG titers were similar in secukinumab treated patients and immunocompetent controls (Figure 1). Conclusion: SpA patients treated with secukinumab consistently demonstrated an adequate humoral response to the BNT162b2 mRNA vaccination similar to immunocompetent controls, both short-term and within six months after two vaccine doses and after the third vaccine dose.
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Background: Data on the kinetics of the immune response to SARS-CoV-2 vaccination in patients with autoimmune infammatory rheumatic diseases (AIIRD) are limited. Objectives: To evaluate the kinetics of the immune response induced by two and three doses of the BNT162b2 mRNA vaccine in adult patients with AIIRD and immunocompetent controls. Methods: A prospective multicenter study investigated the antibody response to the BNT162b2 vaccine by serial measurement of serum anti-SARS-CoV-2 S1/S2 IgG titers at the following time points: 2-6 weeks (AIIRD n=720, controls n=122) and six months (AIIRD n=628, controls=116) after the second vaccine dose, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). A seropositive response was defned as a detectable anti-S1/S2 IgG titer ≥ 15 BAU/ml. T-cell immune response was evaluated in a sample of patients (n=28) and controls (n=9) by intracellular staining of S-stimulated CD4+ T-cells for TNFα and IFNγ production. Results: The two-dose vaccine regimen induced a higher humoral response in controls compared to patients, as refected by the post-vaccination seroposi-tivity rates of 100% vs 84.72%, p<0.0001, and 96.55% vs 74.26%, p<0.0001 at 2-to-6 weeks and at 6 months, respectively. The decline of S1/S2 IgG titers within six months was similar in controls and patients. Following the 3rd vaccine, the seropositivity rate increased to 80.47% and 100% in AIIRD and control groups, p=0.0028, with a signifcantly higher increase of S1/S2 IgG titers in controls compared with AIIRD patients, 284.09±76.58 vs 219.39±151.55 BAU/ml, p=0.0016. At all-time points, S1/S2 IgG titers were signifcantly lower in AIIRD patients compared with controls (Figure 1). We further investigated the impact of therapies on the vaccine's immuno-genicity (Figure 1). Glucocorticoids (GC) were associated with a significantly lower seropositivity rate and lower S1/S2 IgG titers compared to controls at all time points. Monotherapy with methotrexate (MTX) was associated with a comparable to controls humoral response at all time points. Anti-cytokine biologics (TNFi, IL6i, IL17i) were associated with an initial high seropositivity rate, similar to controls, followed by a steeper decline at 6 months, 79.82% vs 96.55%, p=0.0001, and restoration of seropositivity after the 3rd vaccine dose in all patients. JAKi were associated with a mildly decreased seroposi-tivity rate after the 2nd vaccine dose and similar to controls response after the 3rd vaccine dose. Abatacept was associated with a reduced immunogenicity after the 2nd vaccine dose, but was restored to 100% seropositivity after the 3rd vaccine dose. Rituximab (RTX) significantly blunted the humoral response at all time points, with a seropositivity rate of 42% after the 2nd vaccine dose, 29% at 6 months, and with increase to 40% after the 3rd vaccine dose. A third of the RTX-treated patients who were seronegative after two vaccine doses, seroconverted after the 3rd dose. The multivariate model for predicting the seropositive response to vaccination found that higher S1/S2 IgG titers after the 2nd vaccine dose was associated with a higher seropositivity rate following the 3rd vaccine dose, OR 1.026 (1.008-1.045), p=0.0027, and that treatment with RTX was associated with a 14.3-fold risk for a negative humoral response, p≤0.0001. Cellular immune response, evaluated mainly in RTX treated patients, was preserved prior to and after the 3rd vaccine dose and was similar to controls. Conclusion: Over a six-month period, the two dose BNTb262 vaccination was associated with a similar extent of waning of the humoral immune response in AIIRD patients and controls. The 3rd vaccine dose restored the response in all controls and in patients treated with MTX monotherapy, anti-cytokine biolog-ics, abatacept, and JAKi. Treatment with GC and RTX was associated with an impaired humoral response at all time points.
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Introduction: : The safety, efficacy, and immunogenicity data of the vaccine against COVID-19 for adolescents with Juvenile-onset Autoimmune Inflammatory Rheumatic diseases (AIIRD) is currently limited. Vaccinating the immunocompromised adolescents for COVID-19 is particularly valuable to protect this vulnerable population. Objectives: To evaluate the safety and immunogenicity of the BNT162b2 mRNA vaccine in adolescents with AIRD treated with immunosuppressive medications compared with healthy adolescents. Methods: This prospective multicenter study examined the safety and immunogenicity of the two-dose regimen BNT162b2 mRNA vaccine in adolescents aged 12-18 years diagnosed with juvenile-onset AIIRD including Juvenile Idiopathic Arthritis (JIA), connective tissues diseases (CTD) including systemic lupus erythematosus (SLE), systemic vasculitides and uveitis. Patients were evaluated 2-10 weeks after the second dose of the vaccine. Safety and post-vaccination COVID-19 infection were evaluated, as well as disease activity prior and following the vaccine. Post vaccination serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured. Seropositivity was defined as IgG ≥15 binding antibody units (AU/ml). Anti-Nuclear (N) IgG antibodies were measured for evidence of past COVID-19 infection (level above 1.4RLU was considered positive). Results: 71 adolescents with AIIRD patients and 28 controls from 2 countries, 4 centers, participated in the study. The most common diagnosis in the AIIRD cohort was JIA (N=27), followed by SLE (N=14). The mean disease duration was 5.1±4.48 years (N=70). A total 84.5% (N=60) of the patients were treated with immunomodulatory medications. Post vaccination disease activity remained stable in 96.88% of the adolescents with AIIRD, and post vaccination treatment change was made in the minority of the patients (N=3, 4.84%). Both patients and controls have tolerated the vaccine well, with minimal side effects. There were no severe adverse events in both groups. No post vaccination infection with COVID-19 was documented in both groups. Seropositivity rate was 90.32% in adolescents with AIIRD and 100% in the healthy controls (N=28/31 vs. N=14/14;p=0.54). The level of the S1/S2 antibodies was significantly reduced in adolescents with AIIRD compared to controls (mean± SD 218.97±150.9 vs 380.78± 71.89, P<0.0001). The N Index was negative in both adolescents with AIIRD (0.09±0.09, [N=15]) and healthy controls (0.054±0.036 [N=11]), indicating that none of these participants suffered from past COVID- 19 infection. Conclusion: In our cohort, the BNTb262 mRNA COVID-19 vaccine was shown to have excellent safety profile in immunocompromised adolescents with Juvenile-onset AIIRD, with mild post vaccination side effects, similar to the safety profile of the healthy controls. No post vaccination COVID-19 illness was documented. Post vaccination disease activity was mostly kept stable. Immunogenicity was very good in both groups, with significantly higher S antibody titers in the healthy controls.
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OBJECTIVES: To assess the prevalence of anti-SARS-CoV-2 antibodies in autoimmune inflammatory rheumatic disease (AIIRD) patients, and to define clinical factors associated with seropositivity. METHODS: A cross sectional study was conducted at a tertiary rheumatology department in Israel. Consecutive patients completed a questionnaire and were tested for SARS-CoV-2 anti-nucleoprotein IgG (N-IgG). If this was positive, an anti-S1/S2 spike IgG (S-IgG) test was done. If both were positive, the patient was considered seropositive. Seropositive patients were retested after 3 months. RESULTS: The study included 572 AIIRD patients. Thirty patients were found seropositive, for a seroprevalence of 5.24%. The seropositive rate was significantly lower for patients treated with immunosuppressive medications (3.55%, p<=0.01), and specifically for patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) (2.7%, p<=0.05). These associations remained significant in the multivariate regressions adjusting for age, sex and exposure to a known COVID-19 patient. A second serology test 3 months later was collected in 21 of the 30 seropositive patients. In a mean+/-standard deviation (SD) of 166.63+/-40.76 days between PCR and second serology, 85% were still positive for N-IgG, and 100% were still positive for S-IgG, with a higher mean+/-SD titre compared to the first S-IgG (166.77+/-108.77 vs. 132.44+/-91.18, respectively, p<=0.05). CONCLUSIONS: Humoral response to SARS-CoV-2 in AIIRD patients may be affected be immunosuppressive treatment, especially bDMARDs. In patients with AIIRD, titres of SARS-CoV-2 IgG antibodies, especially N-IgG antibodies, fade with time, while S-IgG antibodies persist.
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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. Preand 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. 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.
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Background: Immune responses in AIIRD patients may be reduced and influenced by immunosuppressive treatments[1].The effect of immunosuppression on the mounting of SARS-CoV-2 antibodies in AIIRD is not clear. Objectives: To assess the prevalence of SARS-CoV-2 antibodies in AIIRD patients and to define clinical factors affecting this prevalence. Methods: Consecutive consenting AIIRD patients from the Rheumatologic department in Tel Aviv Medical Center participated in the study. Patients answered a questionnaire and were tested for SARS-CoV-2 antibodies. A two stage antibody testing was done in order to increase specificity. Results: The study included 560 AIIRD patients (229 RA, 149 PsA, 84 SLE, 55 vasculitidies, 40 SpA, 3 other CTD), of them 26 patients were found to have SARS-CoV-2 IgG antibodies (4.6%) (Table 1). This was more than double than aprevious prevalence in the same clinic population studied after the first wave of the pandemic in Israel, which was 2.07% (accepted for publication). A lower rate of immunosuppression was found for positive SARS-CoV-2 IgG patients compared to negative serology patients (Table 1, p=0.009). There was also a trend for the subgroup of patients on biologic DMARDS (26.92% vs. 47% respectively, p=0.06). Positive SARS-CoV-2 PCR test was reported and confirmed in 36 patients, of them 14 (38.89%) had negative serology. Patients who did not have antibodies had numerically more than double rates of glucocorticoids and bDMARDs treatment. The time between positive PCR test to positive serology test was significantly shorter (mean±standart deviation 75.57±40.44 days) than the time between positive PCR to negative serology test (130.79±86.47 (p=0.04) (Table 1 and Figure 1) suggesting a fading of the antibody response with time. Conclusion: The prevalence of SARS-CoV-2 IgG was 4.6% in a population of AIIRD patients from a single tertiary medical center in Israel. SARS-CoV-2 seroprevalence tended to be low among AIIRD patients on immunosuppressive treatment, including in patients with a confirmed history of positive SARS-CoV-2 PCR, similar to other studies [3]. As in individuals without AIIRD, the mounting of SARS-CoV-2 IgG seems to fade with time. Larger studies are needed to confirm the potential effect of immunosuppression on the antibody response in AIIRDs.