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

Abstract

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

Kinetics of Anti-SARS-CoV-2 Antibody Responses 3 Months Post Complete Vaccination with BNT162b2; A Prospective Study in 283 Health Workers

“…The presence of comorbidities may impair the anticipated immunogenicity following COVID-19 vaccination [30][31][32][33]. Relatively lower NAbs titers were observed among individuals with diabetes at D22.…”

B cell numbers predict humoral and cellular response upon SARS-CoV-2 vaccination among patients treated with rituximab

“…However, in particular under B cell depleting therapy with RTX, hampered humoral and cellular responses following influenza, pneumococcal and hepatitis B vaccination have been reported [11][12][13][14][15][16] . Data available about SARS-CoV-2 vaccine response in rituximab treated AIIRD patients reveal substantially impaired humoral [17][18][19] but partly inducible cellular immune responses 20 . However, little is known about the complex mechanisms between T, B and plasma cells, as well as the level of B cell repopulation necessary for proper vaccine response among RTX patients.…”

Anti-COVID-19 Vaccination in Patients with Autoimmune-Autoinflammatory Disorders and Primary/Secondary Immunodeficiencies: The Position of the Task Force on Behalf of the Italian Immunological Societies

“…Spiera [109]. Finally, Furer et al, in the largest multicentric study carried out in Israel on 686 patients immunized with two doses of Comirnaty Pfizer vaccine, observed a severely reduced immune response in patients under rituximab and a moderately reduced immune response in patients on CCS, abatacept, and mycophenolate mofetil, whereas only a mild impairment of immune response was observed because of MTX [93]. Thus, (even with mRNA vaccines) analogous to what has been observed with traditional vaccines, patients with AIAIDs may present a reduced vaccine-induced immune response because of the disease itself as well as immunosuppressive therapy, with CCS and anti-CD20 mAbs nearly always implicated in the immunosuppressive effect.…”

“…Further studies, including a larger sample of these patients, treated with different immunosuppressive drugs, and analyzed during a longer period, are mandatory. Despite the current lack of definitive recommendations, some preliminary studies [48][49][50], supported by a recent larger multicenter study [93], confirm that mRNA vaccines seem to be well tolerated in patients with AIAIDs, without the induction of flare-ups or more frequent and serious AEs than in the general population. Recently, herpes zoster appearance was described in 6/491 (1.2%) patients with IMIDs (Immune-Mediated Inflammatory Disorders) following an mRNA vaccine [94].…”

“…However, the limits on the use of immunosuppressive drugs in the vaccination period have been based on very few studies on traditional vaccines, generally counterbalanced by a higher number of reports, which did not show any significant negative interference in the immune response to vaccines, thus providing an explanation of the divergent recommendations. Recently, some studies have been published on the immune response to two-dose anti-COVID-19 mRNA vaccines in patients with AIAIDs under immunosuppressive therapy [49,50,93,[107][108][109]. Geisen et al reported that the immune response was adequate in 26 patients with chronic inflammatory conditions under immunosuppressive therapy [49]; Simon et al studied 84 patients with AIAIDs and 10% of the patients were unable to respond vs. 1% of the healthy controls; moreover, such a reduced response was ascribed to the disease itself and not to the immunosuppressive therapy [50].…”