ABSTRACT
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.
ABSTRACT
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.
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. 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.