Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study

Victoria Furer, Tali Eviatar, Devy Zisman, Hagit Peleg, Daphna Paran, David Levartovsky, Michael Zisapel, Ofir Elalouf, Ilana Kaufman, Roni Meidan, Adi Broyde, Ari Polachek, Jonathan Wollman, Ira Litinsky, Katya Meridor, Hila Nochomovitz, Adi Silberman, Dana Rosenberg, Joy Feld, Amir Haddad, Tal Gazzit, Muna Elias, Nizar Higazi, Fadi Kharouf, Gabi Shefer, Orly Sharon, Sara Pel, Sharon Nevo, Ori Elkayam, Victoria Furer, Tali Eviatar, Devy Zisman, Hagit Peleg, Daphna Paran, David Levartovsky, Michael Zisapel, Ofir Elalouf, Ilana Kaufman, Roni Meidan, Adi Broyde, Ari Polachek, Jonathan Wollman, Ira Litinsky, Katya Meridor, Hila Nochomovitz, Adi Silberman, Dana Rosenberg, Joy Feld, Amir Haddad, Tal Gazzit, Muna Elias, Nizar Higazi, Fadi Kharouf, Gabi Shefer, Orly Sharon, Sara Pel, Sharon Nevo, Ori Elkayam

Abstract

Introduction: Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.

Methods: A multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). 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. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose.

Results: Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients.

Conclusion: mRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.

Keywords: Covid-19; biological therapy; methotrexate; rituximab; vaccination.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Cumulative seropositive rate according to the interval (days) between the last course of rituximab administration and BNT1622b vaccination. mRNA, messenger RNA.
Figure 2
Figure 2
Disease activity scores before and after completing two doses of BNT162b2 vaccine. Data on prevaccination and postvaccination disease activity measures were available for 165 patients with RA-SDAI, 182 patients with RA-CDAI, 164 patients with RA-DAS-28-CRP, 121 patients with PsA-CDAI, 117 patients with PsA-DAPSA, 131 patients with PsA-PASI, 43 patients with AxSpA-ASDAS, 47 patients with AxSpA-BASDAI and 85 patients with SLE-SLEDAI. ASDAS, Ankylosing Spondylitis Disease Activity Score; axSpA, axial spondyloarthritis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CDAI, Clinical Disease Activity Index; DAPSA, Disease Activity in Psoriatic Arthritis; PASI, Psoriasis Area Severity Index; PsA, psoriatic arthritis; RA, rheumatoid arthritis; SDAI, Simplified Disease Activity Index; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Disease Activity Index for SLE.

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