Response to SARS-CoV-2 vaccination in systemic autoimmune rheumatic disease depends on immunosuppressive regimen: a matched, prospective cohort study

Mandl, Péter; Tobudic, Selma; Haslacher, H.; Karonitsch, Thomas; Mrak, Daniel; Nothnagl, Thomas; Perkmann, Thomas; Radner, Helga; Sautner, Judith; Simader, Elisabeth; Winkler, Florian; Burgmann, Heinz; Aletaha, Daniel; Winkler, Stefan; Blüml, Stephan

doi:10.1136/annrheumdis-2021-221788

Cited by 17 publications

(28 citation statements)

References 34 publications

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“…Participants with autoimmune diseases usually obtain immunosuppressive drugs. Thus, this finding can be considered consistent with other reports, showing significantly lower antibody response after vaccination among participants with immunosuppression [ 9 , 17 , 18 ] and underlining the potential negative effect of immunosuppressive drugs in this context [ 8 , 18 ].…”

Section: Discussionsupporting

confidence: 92%

Serological Response and Relationship with Gender-Sensitive Variables among Healthcare Workers after SARS-CoV-2 Vaccination

Cangemi

Franco²,

Angeloni³

et al. 2022

JPM

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Vaccine-induced immunity is a key strategy in the long-term control of the COVID-19 pandemic. The aim of our study was to explore the relationship between mRNA vaccine-induced antibodies and gender-sensitive variables among healthcare workers. Two thousand-sixty-five volunteers who received the BNT162b2 vaccine were enrolled in the study and followed up. Demographic, clinical, and social variables (educational level, marital status, occupation, childcare) were evaluated through a self-administered questionnaire. Anti-Spike (S) IgG were measured at 1 month (T1) and at 5 months (T2) after the second vaccine dose. At T1, median anti-S IgG values were 693 [394–>800] AU/mL (1 AU = 2.6 BAU). Values > 800 AU/mL (2080 BAU/mL) were directly associated with a previous COVID-19 (p < 0.001) infection and inversely with age (p < 0.001), smoking habit (p < 0.001), and autoimmune diseases (p < 0.001). At T2, a significant decreasing in anti-S IgG values was observed (187 [81–262] AU/mL), with a median decrease of 72 [60–82]%. On multivariate data analysis, a reduction of more than 82% was directly associated with male sex (p < 0.021), age (p < 0.001), smoking (p = 0.038), hypertension (p = 0.042), and, inversely, with previous COVID-19 infection (p < 0.001) and being “cohabiting” (p = 0.005). Our findings suggest that demographic, clinical, and social variables play a role in anti-S IgG values decreasing in long-term follow up and should be considered to find personalized vaccine schedules.

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Section: Discussionsupporting

confidence: 92%

Serological Response and Relationship with Gender-Sensitive Variables among Healthcare Workers after SARS-CoV-2 Vaccination

Cangemi

Franco²,

Angeloni³

et al. 2022

JPM

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“…Consistent with the study by Frey et al , patients on DMARD monotherapy had higher antibody titres than those on combination therapy 5. A recent study by Mandl et al also showed that treatment with GCs in combination with other treatments had a negative impact on the seroconversion rate and the overall antibody level following vaccination 26…”

Section: Discussionsupporting

confidence: 66%

Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study

et al. 2022

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ObjectivesTo evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls.MethodsA prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2–6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2–6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample.ResultsThe two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, p<0.0001, and 96.55% versus 74.26%, p<0.0001 at 2–6 weeks and at 6 months, respectively. The third vaccine dose restored the seropositive response in all controls and 80.47% of patients with AIIRD, p=0.0028. All patients treated with methotrexate monotherapy, anticytokine biologics, abatacept and janus kinase (JAK) inhibitors regained the humoral response after the third vaccine, compared with only a third of patients treated with rituximab, entailing a 16.1-fold risk for a negative humoral response, p≤0.0001. Cellular immune response in rituximab-treated patients was preserved before and after the third vaccine and was similar to controls. Breakthrough COVID-19 rate during the Delta surge was similar in patients and controls, 1.83% versus 1.43%, p=1.ConclusionsThe two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.

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“…Although many patients with IMID mount adequate serological responses to vaccination after 2 doses of an mRNA vaccine, a proportion of patients with IMID show reduced responses compared with healthy controls (7)(8)(9)(10)(11)(12)(13)(14), as confirmed in recent meta-analyses (15,16). Patients receiving glucocorticoids, methotrexate (MTX), mycophenolate, anti-TNF, and B cell-depleting therapy may have attenuated serological responses to COVID-19 vaccines (7,11,13,15,(17)(18)(19)(20)(21)(22)(23)(24). Moreover, 2 recent studies showed that patients on anti-TNF therapy have greater waning of humoral immunity compared with healthy controls (13,21).…”

Section: Introductionmentioning

confidence: 91%

Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases

Dayam¹,

Law²,

Goetgebuer³

et al. 2022

JCI Insight

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The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a serious health crisis (1, 2). COVID-19 infections vary from asymptomatic or mild through to severe disease, with lethal complications such as progressive pneumonia, acute respiratory distress syndrome, and BACKGROUND. Limited information is available on the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID).METHODS. This observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic disease, with or without maintenance immunosuppressive therapies. Ab and T cell responses to SARS-CoV-2, including neutralization against SARS-CoV-2 variants, were determined before and after 1 and 2 vaccine doses. RESULTS.We prospectively followed 150 subjects, 26 healthy controls, 9 patients with IMID on no treatment, 44 on anti-TNF, 16 on anti-TNF with methotrexate/azathioprine (MTX/AZA), 10 on anti-IL-23, 28 on anti-IL-12/23, 9 on anti-IL-17, and 8 on MTX/AZA. Ab and T cell responses to SARS-CoV-2 were detected in all participants, increasing from dose 1 to dose 2 and declining 3 months later, with greater attrition in patients with IMID compared with healthy controls. Ab levels and neutralization efficacy against variants of concern were substantially lower in anti-TNF-treated patients than in healthy controls and were undetectable against Omicron by 3 months after dose 2. CONCLUSIONS.Our findings support the need for a third dose of the mRNA vaccine and for continued monitoring of immunity in these patient groups.FUNDING. Funded by a donation from Juan and Stefania Speck and by Canadian Institutes of Health (CIHR)/COVID-Immunity Task Force (CITF) grants VR-1 172711 and VS1-175545 (to THW and ACG), CIHR FDN-143250 (to THW), GA2-177716 (to VC, ACG, and THW), and GA1-177703 (to ACG) and the CIHR rapid response network to SARS-CoV-2 variants, CoVaRR-Net (to ACG).

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Response to SARS-CoV-2 vaccination in systemic autoimmune rheumatic disease depends on immunosuppressive regimen: a matched, prospective cohort study

Cited by 17 publications

References 34 publications

Serological Response and Relationship with Gender-Sensitive Variables among Healthcare Workers after SARS-CoV-2 Vaccination

Serological Response and Relationship with Gender-Sensitive Variables among Healthcare Workers after SARS-CoV-2 Vaccination

Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study

Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases

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