Efficacy and tolerability of a third dose of an mRNA anti-SARS-CoV-2 vaccine in patients with rheumatoid arthritis with absent or minimal serological response to two previous doses

Schmiedeberg, Kristin; Vuilleumier, Nicolas; Pagano, Sabrina; Albrich, Werner C.; Ludewig, Burkhard; Kempis, Johannes von; Rubbert-Roth, Andrea

doi:10.1016/s2665-9913(21)00328-3

Cited by 34 publications

(38 citation statements)

References 10 publications

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“…The large number of patients with ARD and the inclusion of an age-balanced and sex-balanced CG are relevant strengths of the present study and provided a sizeable sample to evaluate humoral response to additional vaccine dose and the impact of the drugs. In fact, the few studies focusing on the third dose for immunocompromised individuals were small-sized17 50 or did not have a control group 24 25 28–30 44 46…”

Section: Discussionmentioning

confidence: 99%

“…15 There is increasing evidence on the efficacy of a third dose of vaccine in enhancing protective effect. [16][17][18][19] However, data on CoronaVac are limited. A study in healthy adults demonstrated a strong humoral booster following an additional dose administered 8 months after the primary schedule, indicating an efficient recalling of SARS-CoV-2-specific immune memory.…”

Section: Introductionmentioning

confidence: 99%

“…23 24 Regarding ARD population, there is one case series reporting that a third dose of mRNA vaccine induced seroconversion in almost 90% of 17 patients with rheumatoid arthritis with minimal response to primary vaccination. Most of them discontinued disease modifying anti-rheumatic drugs (DMARD) temporarily to receive the third dose 17 and more data are necessary.…”

Section: Introductionmentioning

confidence: 99%

“…There is increasing evidence on the efficacy of a third dose of vaccine in enhancing protective effect 16–19. However, data on CoronaVac are limited.…”

Section: Introductionmentioning

confidence: 99%

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Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases

et al. 2022

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ObjectiveTo determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response.MethodsAdult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination.ResultsARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001).ConclusionsWe provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX.Trial registration numberNCT04754698.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…There is increasing evidence on the efficacy of a third dose of vaccine in enhancing protective effect 16–19. However, data on CoronaVac are limited.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases

et al. 2022

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“…While official policy recommendations do not include antibody testing as part of the vaccination programs, serological surveillance has been included in several pilot settings, and many studies have already established the extent and magnitude of antibody response following administration of COVID mRNA vaccines ( 7 – 9 ). These studies, mostly performed in selected patient groups, have demonstrated an impaired humoral immune response in kidney transplant recipients ( 10 ), patients on renal replacement therapy ( 11 ) and after solid organ and lung transplantation ( 12 , 13 ), patients living with human immunodeficiency virus (HIV)-1 infection (HIV, PLWH) ( 14 – 16 ), multiple sclerosis (MS) ( 17 , 18 ) and diagnosed with rheumatoid arthritis ( 19 , 20 ), spondyloarthritis ( 21 ), or inborn errors of immunity ( 22 , 23 ). While antibody responses have already been characterized within vaccinated immunocompromised patients, little is known on the ensuing cellular immune response of vaccine induced antibodies in patients diagnosed with rheumatologic disorders (e.g.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Humoral and Cellular Responses in SARS-CoV-2 mRNA Vaccinated Immunocompromised Patients

et al. 2022

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BackgroundImmunocompromised patients are at increased risk of severe COVID-19 and impaired vaccine response. In this observational prospective study, we evaluated immunogenicity of the BNT162b2 mRNA vaccine in cohorts of primary or secondary immunocompromised patients.MethodsFive clinical groups of immunocompromised patients [primary immunodeficiency (PID) (n=57), people living with HIV (PLWH) (n=27), secondary immunocompromised patients with a broad variety of underlying rheumatologic (n=23) and homogeneous (multiple sclerosis) neurologic (n=53) conditions and chronic kidney disease (CKD) (n=39)] as well as a healthy control group (n=54) were included. Systemic humoral and cellular immune responses were evaluated by determination of anti-SARS-CoV-2 Spike antibodies using a TrimericS IgG assay (Diasorin) and through quantification of interferon gamma release in response to SARS-CoV-2 antigen with QuantiFERON SARS-CoV-2 assay (Qiagen), respectively. Responses were measured at pre-defined time-points after complete vaccination.ResultsAll healthy controls, PLWH and CKD-patients had detectable antibodies 10 to 14 days (T2) and 3 months (T3) after administration of the second vaccination. In contrast, only 94.5% of the PID, 50.0% of the rheumatologic and 48.0% of neurologic patients developed antibodies at T2 and only 89.1% of the PID, 52.4% of the rheumatologic and 50.0% of neurologic patients developed antibodies at T3. At T3 no significant differences in cellular response between the healthy control group and the PLWH and CKD groups were found, while proportions of reactive subjects were lower in PID and rheumatologic patients and higher in neurologic patients. Humoral and cellular immune responses significantly correlated in the healthy control, PID, PLWH groups for all 3 antigens.ConclusionPatients with acquired or inherited immune disorders may show variable immune responses to vaccination with the BNT162b2 mRNA vaccine against SARS-CoV-2. Whether humoral, cellular or both immune responses are delayed depends on the patient group, therapy and individual risk factors. These data may guide the counselling of patients with immune disorders regarding vaccination of SARS-CoV-2.

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Immunogenicity and Safety of Standard and Third‐Dose SARS–CoV‐2 Vaccination in Patients Receiving Immunosuppressive Therapy

Syversen

Jyssum

Tveter

et al. 2022

Arthritis & Rheumatology

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Objective Immunogenicity and safety following receipt of the standard SARS–CoV‐2 vaccination regimen in patients with immune‐mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2‐dose regimen and a third dose of SARS–CoV‐2 vaccine in IMID patients receiving immunosuppressive therapy. Methods Adult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2‐dose SARS–CoV‐2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor‐binding domain (RBD) of the SARS–CoV‐2 spike protein were performed prior to and 2–4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor‐binding domain of the full‐length SARS–Cov‐2 spike protein, were allotted a third vaccine dose. Results A total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti‐RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192–4,191) than in controls (median 3,355 AU/ml [IQR 896–7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA–1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable. Conclusion IMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.

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Efficacy and tolerability of a third dose of an mRNA anti-SARS-CoV-2 vaccine in patients with rheumatoid arthritis with absent or minimal serological response to two previous doses

Cited by 34 publications

References 10 publications

Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases

Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases

Evaluation of Humoral and Cellular Responses in SARS-CoV-2 mRNA Vaccinated Immunocompromised Patients

Immunogenicity and Safety of Standard and Third‐Dose SARS–CoV‐2 Vaccination in Patients Receiving Immunosuppressive Therapy

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